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PubMed1984

Proteoglycans synthesized by rat ovarian granulosa cells in culture. Isolation, fractionation, and characterization of proteoglycans associated with the cell layer.

Rat ovarian granulosa cells were isolated from immature female rats after stimulation with pregnant mare's serum gonadotropin and maintained in culture. Proteoglycans were labeled with [35S]sulfate, [3H]glucosamine, or [3H]serine as precursors. Proteoglycans associated with the cell layer were extracted with 4 M guanidine HCl buffer containing 2% Triton X-100. Labeled proteoglycans were isolated using sequential DEAE-Sephacel and Sepharose CL-4B chromatography under dissociative conditions in the presence of detergent. The cell layer contained three different hydrodynamic size species of dermatan sulfate proteoglycans, DS-Ic, DS-IIc, and DS-IIIc, and two different hydrodynamic size species of heparan sulfate proteoglycans, HS-Ic and HS-IIc, when analyzed on Sepharose CL-4B, DS-Ic, DS-IIc, and HS-Ic were indistinguishable from corresponding species in the medium fraction in terms of (a) hydrodynamic size analyzed on Sepharose CL-2B or Sepharose CL-4B, (b) buoyant density distribution in dissociative CsCl gradients, and (c) glycosaminoglycan and oligosaccharide compositions. The majority of these three proteoglycan species could be removed by brief trypsin treatment indicating their cell surface localization. Heparin released a part of the trypsin-removable proteoglycan population, which mostly consisted of DS-Ic with smaller amounts of DS-IIc and HS-Ic. Cell layer extracted with 4 M guanidine HCl without detergent contained a large hydrodynamic size structure excluded from Sepharose CL-2B, which contained DS-IIc and HS-Ic proteoglycans with large amounts of exogenous proteins. Proteoglycans were dissociated from this supramolecular structure in the presence of high concentrations of detergents (2% sodium dodecyl sulfate or Triton X-100), indicating the hydrophobic nature of this structure, probably a part of the plasma membrane, and suggesting that DS-IIc and HS-Ic are intercalated into membrane. Both DS-IIIc and HS-IIc were intracellular species, which were not released into the medium by the living cells or removed by either trypsin or heparin. DS-IIIc species was a single glycosaminoglycan chain having the same hydrodynamic size and sulfation pattern as those of glycosaminoglycan chains on DS-II. HS-IIc species was also a single glycosaminoglycan chain with an average molecular size only 1/3-1/4 that of chains on HS-I but heparan sulfate chains from both species showed a similar average sulfation pattern when analyzed by nitrous acid fragmentation. Both DS-IIIc and HS-IIc had small amounts of covalently attached peptides.

Animals↗

PubMed1995

Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep.

Despite the established efficacy of 7.5% NaCl/6% dextran-70 in the treatment of hypovolemia, the optimal formulation of a hyperosmotic/hyperoncotic small volume resuscitation solution has yet to be defined. The present study investigates the cardiovascular effects of hypertonic saline ranging from 3.75%-25% NaCl (HS) and dextran-70 (D-70) ranging from 3 to 24%. HS and D-70 were studied alone or in specific combinations at a dose of 4 mL/kg, in euvolemic sheep. Blood samples were collected before, during and up to 60 min after infusion of the test solutions. Dose-dependent effects of HS were immediate increases in cardiac output (CO) of 30-85%, falling to 10-35% over baseline after 60 min. HS concentrations over 3.75% significantly reduced systemic vascular resistance, but HS had no significant effect on mean arterial pressure (MAP). Plasma volume (PV) expansion with HS was an immediate, but transient increase of 12-35%. Infusion of D-70 induced sustained 10-20% increases in CO and 10-30% increases in PV, peaking 10 min post-infusion. D-70 also resulted in small (5-12 mmHg) increases in MAP. Cardiovascular effects of D-70 correlated with a dose-dependent increase in plasma dextran concentrations. All HS solutions significantly increased plasma Na, which peaked at > or = 200 mEq/L in the 25% group. The effects of D-70 and HS combined were additive on PV expansion and CO. These data indicate that concentrations of HS and D-70 which are higher than those currently used have a greater capability for expanding PV, but use of HS > 7.5% may be limited by resulting hypernatremia.

Animals↗

PubMed1998

Homicide followed by suicide: Paris and its suburbs, 1991-1996.

Homicide-suicides (HS) are relatively infrequent events. Yet, they are of great concern because they often result in the death of family members, young children, and cause additional morbidity, family disruption and childhood psychological trauma. The aims of our study were (a) to examine the sociodemographic, clinical, and autopsy characteristics of HS in Paris and its suburbs from 1991 through 1996, and (b) to analyze the psychodynamic determinants leading up to the onset of HS. Our findings are compared with those obtained in other international studies. For the purpose of the present study. HS was defined as a violent event in which an individual committed homicide and subsequently committed suicide within a few hours. The main results are as follows. During the six-year study period, 56 HS involving 133 victims were investigated at the Institute of Forensic Medicine of Paris. Seventeen events occurred in Paris and 39 in its suburbs. Paris has a population of approximately 2,200,000 while its suburbs are home to another 8,5000,000. Of the 56 offenders, 48 (85%) were males. The mean age of offenders was 51 years in males (range, 24 to 83) and 40.5 years in females (range, 33 to 56). In 45 events (80%), the offenders used a gun for both the homicide and suicide. A knife was used in only 4 murders, strangulation in 4 other cases, with poisoning, arson, or beating occurring in one case each. In 9 cases, the offender used a different weapon for homicide and suicide. Among firearms, handguns were more likely to be used (26 cases) than shotguns (6 cases) or rifles (13 cases). In 40 cases the offender killed one victim, in 11 cases 2 victims, and in 5 cases 3 victims. The homicide victims consisted of 34 children (21 boys), mean age 8 years (range, 1 to 16), 29 spouses (26 females), 2 girlfriends, 10 strangers, and 2 relatives. Five pets were killed. HS were most likely to be committed in the home. A suicide note was found near the victims in 29 cases (50% of events). In 42 cases the offender was found to be severely depressed. Familial HS were the most frequent events followed by suicidal pacts. When male sexual proprietariness and amorous jealousy were involved, the HS perpetrators acted often impulsively in carrying out the HS. There had been a chronically chaotic relationship and frequent physical violence and verbal threats. The triggering event was often the female withdrawal or estrangement. Only in a few cases, other motivations such as occupational or money problems were involved. Chronic alcoholism was found in 16 cases. In conclusion, the offender was more likely to be a male, severely depressed, violent and jealous who killed his spouse, and often his children, with impulsiveness, but after numerous threats. Our findings suggest that HS differ from both homicide and suicide and thus occupy a distinct epidemiological domain requiring specific prevention programs.

Adolescent↗

PubMed1998

Description and targeted deletion of 5' hypersensitive site 5 and 6 of the mouse beta-globin locus control region.

The most upstream hypersensitive site (HS) of the beta-globin locus control region (LCR) in humans (5' HS 5) and chickens (5' HS 4) can act as an insulating element in some gain of function assays and may demarcate a beta-globin domain. We have mapped the most upstream HSs of the mouse beta-globin LCR and sequenced this region. We find that mice have a region homologous to human 5' HS 5 that is associated with a minor HS. In addition we map a unique HS upstream of 5' HS 5 and refer to this novel site as mouse 5' HS 6. We have also generated mice containing a targeted deletion of the region containing 5' HS 5 and 6. We find that after excision of the selectable marker in vivo, deletion of 5' HS 5 and 6 has a minimal effect on transcription and does not prevent formation of the remaining LCR HSs. Taken together these findings suggest that the most upstream HSs of the mouse beta-globin LCR are not necessary for maintaining the beta-globin locus in an active configuration or to protect it from a surrounding repressive chromatin environment.

Animals↗

PubMed1998

Structurally specific heparan sulfates support primitive human hematopoiesis by formation of a multimolecular stem cell niche.

Stem cell localization, conservation, and differentiation is believed to occur in niches in the marrow stromal microenvironment. Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation of the stem cell niche. We compared the structure and function of HS from M2-10B4, a hematopoiesis-supportive cell line, with HS from a nonsupportive cell line, FHS-173-We. Long-term culture-initiating cell (LTC-IC) maintenance was enhanced by PG from supportive cells but not by PG from nonsupportive cells (P <.005). The supportive HS were significantly larger and more highly sulfated than the nonsupportive HS. Specifically, supportive HS contained higher 6-O-sulfation on the glucosamine residues. In agreement with these observations, purified 6-O-sulfated heparin and highly 6-O-sulfated bovine kidney HS similarly maintained LTC-IC. In contrast, completely desulfated heparin, N-sulfated heparin, and unmodified heparin did not support LTC-IC maintenance. Moreover, the supportive HS promoted LTC-IC maintenance but not differentiation of CD34(+)/HLA-DR- cells into colony-forming cells (CFCs) and mature blood cells. The supportive HS but not the nonsupportive HS bound both cytokines and matrix components critical for hematopoiesis, including interleukin-3 (IL-3), macrophage inflammatory protein-1 (MIP-1), and thrombospondin (TSP). Significantly more CD34(+) cells adhered directly to immobilized O-sulfated heparin than to N-sulfated or desulfated heparin. Thus, hematopoiesis-supportive stromal HSPG possessing large, highly 6-O-sulfated HS mediate the juxtaposition of hematopoietic progenitors with stromal cells, specific growth-promoting (IL-3) and growth-inhibitory (MIP-1 and platelet factor 4 [PF4]) cytokines, and extracellular matrix (ECM) proteins such as TSP. We conclude that the structural specificity of stromal HSPG that determines the selective colocalization of cytokines and ECM components leads to the formation of discrete niches, thereby orchestrating the controlled growth and differentiation of stem cells. These findings may have important implications for ex vivo expansion of and gene transfer into primitive hematopoietic progenitors.

Antigens, CD34↗

PubMed2025

Protective effects of liver-derived apolipoprotein A1 against heat stress-induced hypothalamic lipid metabolism and blood-brain barrier integrity.

Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood-brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways-especially glycerophospholipid (GP) metabolism-in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood-brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood-brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.

Blood-Brain Barrier↗

PubMed2026

Associations of Active and Passive Smoke Exposure and Hidradenitis Suppurativa in the Pediatric Population: A Case-Control Study.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory condition associated with cysts of the folliculopilosebaceous unit primarily affecting intertriginous areas. HS has been correlated with smoke exposure in the adult population, but there is a knowledge gap in understanding its effect in pediatric and adolescent patients. This study assesses correlations between active and passive smoke exposure and the development of HS in the pediatric and adolescent population. METHODS: A retrospective case-control study was conducted at Mayo Clinic (2010-2023) of patients diagnosed with HS before the age of 18 years who were age-, sex-, and race-matched to healthy controls in a 1:3 ratio, analyzed using Fisher exact for categorical variables and Kruskal-Wallis for continuous. RESULTS: One hundred and seventy-four cases and 522 controls met inclusion criteria. The prevalence of active and passive smoke exposure was significantly higher in patients with HS compared to controls (p = 0.001), with passive smoke accounting for 64.6% (N = 31/48) of smoke exposure in patients with HS. Smoke exposure was associated with a significant increase in the odds of an HS diagnosis, with an odds ratio of 4.8 (95% CI: 3.06-7.61) for passive and/or active exposure, and 1.64 (95% CI: 1.01-2.61) for passive exposure alone. Smoke exposure was associated with a later age of diagnosis than those with no smoke exposure (p < 0.001). CONCLUSION: Prevalence of active and passive smoke exposure was higher in pediatric and adolescent patients with HS compared to age, sex, and race-matched healthy controls. Smoke exposure increased the odds of having HS and was associated with a later age at diagnosis.

HS↗

PubMed2002

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis.

BACKGROUND: Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. OBJECTIVE: To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. PATIENTS AND METHODS: One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. RESULTS: Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. CONCLUSIONS: Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.

Adolescent↗

PubMed2006

Randomized controlled trial of harmonic scalpel use during thyroidectomy.

OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical complications of thyroidectomy when using the harmonic scalpel (HS) vs conventional hemostasis (CH). DESIGN: Single-blind, randomized controlled trial. SETTING: Department of Surgery, S. Chiara Hospital, University of Pisa, Pisa, Italy. PATIENTS: One hundred patients undergoing thyroidectomy. MAIN OUTCOME MEASURES: Postoperative pain, drainage volume, hypocalcemia, nerve injury, and operative time. INTERVENTION: Patients underwent total thyroidectomy in which either the HS or CH was used. RESULTS: We found no significant differences between the HS and CH groups at baseline. Postoperative pain was reduced in the HS group at 24 hours (mean visual analog scale score, 3.90 vs 5.30; P<.001) and 36 hours (2.27 vs 3.95; P<.001). Drainage volume was significantly lower in the HS group (40.1 mL vs 75.4 mL; P<.001). Transient hypocalcemia was significantly lower in the HS group (5 patients [10%] vs 16 [32%]; P=.01). No patients experienced nerve injury or permanent hypocalcemia. Mean operative times were shorter in the HS group (40.0 vs 46.7 minutes, P<.001). CONCLUSIONS: Use of the HS may reduce postoperative pain, drainage volume, and transient hypocalcemia in patients undergoing thyroidectomy. Shorter operative times and improved outcomes might justify the cost of the HS compared with that of CH.

Adult↗

PubMed1996

Hunger sensation in patients with compensated and and uncompensated type 1 and type 2 diabetes mellitus.

OBJECTIVE: Diabetic patients (DP) refer increased hunger sensation (HS) when hyperglycemic but not yet ketogenic. As HS shows a within-day (ultradian cyclicity) and intra-day (circadian cyclicity) repetitivity, its recursive pattern was investigated in patients with type 1 and type 2 diabetes mellitus (DM), in compensated and uncompensated metabolic stage. METHOD: HS was approached in its cyclic structure by means of spectral analysis (SA), and in its circadian rhythmicity by means of Single Cosinor analysis (SCA), applied to self-rated scores of HS given every 30 min to their HS (orexigram) by DP. RESULTS: Exaggerated periprandial, interprandial, and/or nocturnal peaks of HS were seen in the orexigram of both the type I and type II DP. Specific alterations in HS periodogram were detected, structurally denoting a relative prevalence of the ultradian components along with the deamplification and loss of the circadian harmonics. DISCUSSION: The increase of HS (hyperorexia) in nonketotic DM may be formally attributed to a mechanism of frequency multiplication and amplitude demodulation in the multifrequency bioperiodic structure which physiologically regulates the recursive pattern to the daily HS in human beings.

Adult↗

PubMed1980

Serum glycoproteins in cancer patients: first report of correlations with in vitro and in vivo parameters of cellular immunity.

Serum levels of proteins previously shown to be elevated [acute-phase proteins (APP)-haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin] or depressed (alpha 2 HS-glycoprotein, prealbumin, albumin) in cancer patients were correlated with tumor extent, in vitro lymphocyte reactivity (LR) to phytohemagglutinin (PHA), and quantitative delayed hypersensivity (DH) to dinitrochlorobenzene (DNCB) in 147 preoperative patients with operable solid malignancies either confined to the primary site or with regional spread only. Compared to 58 normal controls, levels of the APP were significantly elevated, alpha 2 HS-glycoprotein and prealbumin depressed, and albumin levels unchanged in patients with either local or regional tumors. In patients with normal DH to DNCB, the APP were higher and prealbumin was lower than in controls; in patients with impaired DH to DNCB, haptoglobin and alpha 1-acid glycoprotein were higher and alpha 2 HS-glycoprotein and prealbumin lower than in patients with normal DH to DNCB. Albumin levels did not differ from normals in any of the groups. Serum protein levels appeared to be more related to the immune status of the patient than to tumor extent. The levels of the three APP correlated directly with each other but inversely with alpha 2 HS-glycoprotein and prealbumin; levels of alpha 2 HS-glycoprotein and prealbumin correlated directly with each other. Levels of haptoglobin and alpha 1-acid glycoprotein correlated inversely with LR to PHA; however, levels of alpha 2 HS-glycoprotein correlated directly with LR to PHA, and uniquely the levels of alpha 2 HS-glycoprotein and LR to PHA both showed similar changes for each of the four quantitative levels of DH to DNCB measured in the cancer patients. The data show that the proteins studied, except for albumin, correlate inversely (APP) or directly (alpha 2 HS-glycoprotein and prealbumin) with in vitro and in vivo parameters of cellular immunity. The results provide a rationale for attempts to improve depressed cellular immunity by lowering circulating levels of APP, as is being attempted in ongoing trials using plasmapheresis, and assessing the effect of exogenous alpha 2 HS-glycoprotein or prealbumin in patients with low levels of these glycoproteins and depressed cellular immunity. The correlations between serum glycoprotein levels and in vitro and in vivo parameters of cellular immunity lend rationale to investigations of the interactions of serum glycoproteins and blood cells having immunologic function that determine the level of cellular immunity expressed in vivo.

Adult↗

PubMed1986

Heparan sulphate proteoglycan as mediator of some adhesive responses and cytoskeletal reorganization of cells on fibronectin matrices: independent versus cooperative functions.

Fibronectin is a multifunctional glycoprotein which promotes the adhesion of a variety of cell types to extracellular matrices, including artificial tissue culture substrata. Biochemical analyses of substratum adhesion sites indicated important functions for cell-surface heparan sulphate proteoglycan (HS-PG) in directly mediating adhesive responses by the binding of heparan sulphate sequences to fibronectin. In addition, fibronectin has a binding domain for a cell surface 'receptor' (possibly a 140K glycoprotein) important in these responses. To differentiate the relative importance of these two binding activities, a proteolytically generated cell-binding fragment of fibronectin has been isolated which binds to the 140K 'receptor' but not to HS or to collagen. Platelet factor 4 (PF4), a tetravalent HS-binding protein, provides a model of the tetravalent HS-binding activity of fibronectin, as supported by affinity chromatography studies (these studies also reveal the complexity of HS-PG metabolism in adhesion sites). Responses are measured on substrata coated with the cell-binding fragment of fibronectin, intact fibronectin, or PF4, singly or in combination. Fibroblast-like BALB/c 3T3 cells form both close and tight-focal adhesive contacts with associated microfilament stress fibres on intact fibronectin. Whereas HS-PG binding appears to mediate the formation of close contacts and linear microfilament bundles, a cooperative relationship exists between the HS- and the cell-binding activities of the intact fibronectin molecule in the formation of focal contacts and stress fibres. Human dermal fibroblasts generate different adhesive responses on HS-binding or cell-binding substrata, which are dependent on whether cells have been grown in medium with ascorbate to maximize production of their own collagenous matrix. As with 3T3 cells, focal contact and stress fibre formations of dermal cells require both binding activities in the intact fibronectin molecule. A third system consists of neuroblastoma tumour cells which adhere and extend neurites on fibronectin. Cell-body adherence, but not neurite extension, occurs on HS-binding matrices whereas neurite extension requires only fibronectin's cell-binding activity; the responses of primary peripheral neurons were exactly the opposite and CNS neurons did not respond at all. These studies indicate the diversity of molecular mechanisms by which various cells interact with the multifunctional fibronectin molecule in order to perform specialized functions, as well as the independent or cooperative functions of heparan sulphate proteoglycan on the cell surface in mediating these responses.

Animals↗

PubMed2002

Effects of humic substances on the bioavailability and aerobic biodegradation of polychlorinated biphenyls in a model soil.

The very high hydrophobicity of polychlorinated biphenyls (PCBs) strongly reduces their bioavailability in aged contaminated soils, thus limiting their bioremediation. The biodegradability of PCBs in heavily contaminated soils can be significantly enhanced by soil treatment with surface-active agents. In this work, the effects of naturally occurring surfactants such as humic substances (HS) on the aerobic biodegradation of PCBs in a model soil were studied. The soil was amended with biphenyl (4 g/kg), Fenclor 42 (1,000 mg/kg), the aerobic PCB-biodegrading bacterial co-culture ECO3 (inoculum: 10(8)CFU/mL), and treated in aerobic batch slurry-phase conditions (17.5% w/v) with and without the addition of HS at the rates of 1.5 and 3.0% (w/w). Low PCBs biodegradation and dechlorination yields were observed in the HS-free microcosms, probably as a result of the rapid disappearance of inoculated bacteria. The presence of HS influenced significantly the activity of the specialized biomass and the biodegradation of PCBs in the microcosms. The microcosms that received HS at the 1.5% rate showed a higher persistence of the specialized bacteria and yields of PCB biodegradation and dechlorination about 150 and 100%, respectively, larger than those found for the HS-free microcosms. Lower stimulating effects were observed in the microcosms added with the HS at 3.0% rate. These effects were attributed to an increased solubilization of PCBs in the hydrophobic domains of the humic supramolecular associations and to a different accessibility of PCBs by the specialized bacteria at the different rates of HS addition. Although the slurry-phase treatment generally showed a decrease of the original soil ecotoxicity, the addition of the originally non-toxic HS decreased soil ecotoxicity for the Collembola animal biomarker and increased that towards the Lepidium sativum vegetal biomarker.

Aerobiosis↗

PubMed2007

Raised C-reactive protein levels in patients with recent onset type 1 diabetes.

BACKGROUND: To investigate serum concentrations of high-sensitive C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12). METHODS: CRP and AGP were measured in 44 recent onset T1DM patients (26M/18F, mean age 14.9 +/- 9.1 years), and 44 age- and sex-matched controls, using a highly sensitive immunonephelometric assay. RESULTS: There were no significant differences in the concentrations of high-sensitive C-reactive protein (hs-CRP) and AGP between patients and controls. hs-CRP levels significantly increased in patients at T12 compared to the levels at diagnosis [0.69 (0.14-15.5) versus 0.43 (0.14-7.47) mg/L, p < 0.05; for males: 0.77 (0.14-15.5) versus 0.35 (0.14-7.47) mg/L, p < 0.05; for females the increase was not significant]. AGP levels were not different at T12 compared to diagnosis. No significant correlations were found between hs-CRP and body mass index (BMI), C-peptide, glycosylated haemoglobin, or insulin dose. A strong correlation was found between hs-CRP values at diagnosis and those at T12 (rho = 0.73, p < 0.001); indeed, patients with hs-CRP levels above the 50th percentile at diagnosis showed significantly increased hs-CRP values at T12 compared to patients with baseline hs-CRP levels under the 50th percentile [1.61 (0.18-15.5) versus 0.16 (0.14-1.92) mg/L, p < 0.0001)], and to controls [0.55 (0.14-6.50), p = 0.001]. CONCLUSIONS: This is the first report showing that, despite good metabolic control, 1 year of overt T1DM is sufficient to increase hs-CRP levels, especially in males. hs-CRP levels at diagnosis is a predictor for the values observed at 12 months, suggesting the possibility to select a subgroup of patients requiring strict follow-up for cardiovascular complications.

Adolescent↗

PubMed2005

RAD6 gene is involved in heat shock induction of bleomycin resistance in Saccharomyces cerevisiae.

Cells react to environmental and endogenous challenges such as high temperature, reactive oxygen species, DNA damage, and nutrient starvation by activating several defense mechanisms known as stress responses. An important feature is the overlap between different stress responses that contributes at least in part to the phenomenon of cross-protection. We previously demonstrated that pretreatment with a heat shock (HS) induces resistance to the lethal and mutagenic effects of the antineoplastic drug Bleomycin (BLM) in wild-type Saccharomyces cerevisiae. At the DNA level, the HS resulted in more efficient repair of BLM-induced DNA damage. In the present study, we have investigated the mechanisms involved in this HS-induced BLM resistance. Since the RAD6 gene is involved in the ubiquitin system and DNA repair, we analyzed the effects of HS on the lethality of BLM in a rad6Delta (ubc2) mutant strain of S. cerevisiae. The rad6Delta mutant was more sensitive to the lethal effects of BLM than wild-type yeast and HS had no effect on the lethality of BLM in the mutant. Analysis of cell proliferation kinetics indicated that the HS-induced cell cycle delay observed in the wild-type yeast was absent in the rad6Delta mutant strain. BLM treatment impaired mutant cell proliferation, and HS had no effect on the delayed cell kinetics of the mutant. In addition, pulsed-field electrophoresis of chromosomes damaged by BLM indicated that there was very little recovery from damage in the mutant after 24 hr of incubation in BLM-free nutrient medium, and that HS had little effect on the recovery. These data indicate that the RAD6 gene is involved in the HS-induced BLM resistance observed in the isogenic wild-type strain.

Bleomycin↗

PubMed2001

Heat shock-induced thermoprotection of action potentials in the locust flight system.

There is increasing evidence that heat shock (HS) has long-term effects on electrophysiological properties of neurons and synapses. Prior HS protects neural circuitry from a subsequent heat stress but little is known about the mechanisms that mediate this plasticity and induce thermotolerance. Exposure of Locusta migratoria to HS conditions of 45 degrees C for 3 h results in thermotolerance to hitherto lethal temperatures. Locust flight motor patterns were recorded during tethered flight at room temperature, before and after HS. In addition, intracellular action potentials (APs) were recorded from control and HS motoneurons in a semi-intact preparation during a heat stress. HS did not alter the timing of representative depressor or elevator muscle activity, nor did it affect the ability of the locust to generate a steering motor pattern in response to a stimulus. However, HS did increase the duration of APs recorded from neuropil segments of depressor motoneurons. Increases in AP duration were associated with protection of AP generation against failure at subsequent elevated temperatures. Failure of AP generation at high temperatures was preceded by a concomitant burst of APs and depolarization of the membrane. The protective effects of HS were mimicked by pharmacological blockade of I(K+) with tetraethylammonium (TEA). Taken together, these findings are consistent with a hypothesis that HS protects neuronal survival and function via K+ channel modulation.

Action Potentials↗

PubMed1996

Heat stress improves functional recovery and induces synthesis of 27- and 70-kDa heat shock proteins without preserving sarcoplasmic reticulum function in the ischemic rat heart.

Heat stress (HS) and the subsequent expression of heat shock proteins has been shown to enhance post-ischemic functional recovery and reduce infarct size. The purpose of these experiments was to determine if HS pre-treatment preserves sarcoplasmic reticulum (SR) function, a cellular organelle that plays an important role in myocardial contractility. Anesthetized rats were heat stressed for 15 min by raising temperature to 42 degrees C. Twenty-four hours later the hearts were perfused by Langendorff's method and subjected to either 20 or 35 min of global ischemia, with a subset of hearts then being subjected to 10 or 20 min of reperfusion, respectively. SR function was assessed by oxalate-supported Ca2+ uptake rate in cell free preparations in the presence and absence of ruthenium red, a selective SR calcium release channel blocker Ca2+ uptake decreased significantly from 25.6 +/- 3.4 to 13.4 +/- 1.9 and 11.3 +/- 2.3 nmol/min/mg protein (mean +/- S.E.), following 20 and 35 min of ischemia, respectively. A similar trend was observed following reperfusion as well. No significant difference in Ca2+ uptake was observed between HS v control hearts. Similarly, in samples where the Ca2+ release channel was blocked with ruthenium red, decreased Ca2+ uptake rates were noted after both ischemia and reperfusion, with no significant differences seen between HS and non-HS hearts. There was significant improvement it developed pressure. +dP/dt and -dP/dt, with reduced creatine kinase release in HS v non-HS hearts. Western blot analysis demonstrated increased synthesis of 27- and 70-kDa heat shock proteins in HS but not in control animals. It is concluded that HS improves functional recovery and induces expression of 27- and 70-kDa heat shock proteins without preservation of SR function in the globally ischemic rat heart.

Animals↗

PubMed2002

Modulation of microvascular signaling by heparan sulfate matrix: studies in syndecan-4 transgenic mice.

The onset of tissue ischemia is associated with significant changes in the expression of heparan sulfate- (HS) carrying core proteins that, in turn, lead to alterations in composition of the extracellular HS matrix. Since HS can bind numerous growth factors and cytokines, such changes in the HS matrix content can have profound effects on the ability of these factors to interact with their target cells. To investigate the role of increased HS matrix content on microvascular function, we used alpha-myosin heavy chain (MHC) promoter to overexpress a HS-carrying core protein, syndecan-4, in cardiac myocytes in mice. Mice expressing the transgene (alpha MHC-S4) demonstrated a significant increase in nitric oxide (NO) release in the coronary effluent in response to fibroblast growth factor 2 (FGF2, 1 microg/mL) administration despite similar expression levels of NO synthase genes II and III (iNOS and eNOS, respectively). In vitro studies of coronary microvessels derived from alpha MHC-S4 mice demonstrated increased relaxation response to FGF2 compared to control mice. At the same time, vasodilator response to adenosine diphosphate (ADP) was significantly impaired in alpha MHC-S4 mice-derived microvessels. Addition of exogenous HS to microvessels derived from control mice enhanced FGF2-induced vasodilation while inhibiting ADP-induced vasomotion. The vasomotor activity of the endothelial receptor-independent agent (A23187) and the endothelium-independent agent (sodium nitroprusside) was not affected by heparan sulfate. These results demonstrate that alterations in HS production have a profound and heterogeneous effect on endothelial receptor-dependent vasodilators and point to a novel role of the HS matrix in regulation of microvascular homeostasis.

Adenosine Diphosphate↗