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Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside-dependent and independent effects.

Special extracts from the roots of Harpagophytum procumbens (Devil's Claw) are used in the supportive treatment of inflammatory diseases, and the iridoid derivative harpagoside is thought to be the active principle. To investigate, whether Harpagophytum extracts may also be useful therapeutics in the treatment of inflammatory kidney diseases, we studied the effects of two different extracts containing 8.9% (extract 1) and 27% harpagoside (extract 2), respectively, on IL-1beta-induced nitric oxide (NO) formation as well as transcriptional regulation of inducible NO synthase (iNOS) in rat renal mesangial cells. We observed a concentration-dependent suppression of nitrite formation by about 80%, which was due to an inhibition of iNOS expression. Moreover, a reduction of iNOS promoter activity and nuclear NF-kappaB translocation was observed, indicating that the extracts interfere with the transcriptional activation of iNOS. Three further Harpagophytum extracts containing about 2% harpagoside did not inhibit NO formation suggesting, that only extracts with a high harpagoside content elicit iNOS inhibition. However, pure harpagoside was only inhibitory at concentrations between 0.3 and 1 mg/ml, which is much higher than the harpagoside content present in an effective concentration of the total extracts. Moreover, a harpagoside-free extract 1 also markedly inhibited iNOS expression, indicating that other extract constituents are involved in this effect. Extract 1 exerted a strong antioxidative effect, whereas no such effect could be demonstrated for harpagoside. Together, these data show that special Harpagophytum extracts may represent potential antiinflammatory drugs in the treatment of glomerular inflammatory diseases.

Animals↗

Functional lipidomics: the roles of specialized lipids and lipid-protein interactions in modulating neuronal function.

Lipids fulfill multiple specialized roles in neuronal function. In brain, the conduction of electrical impulses, synaptic function, and complex signaling pathways depend on the temporally and spatially coordinated interactions of specialized lipids (e.g., arachidonic acid and plasmalogens), proteins (e.g., ion channels, phospholipases and cyclooxygenases) and integrative lipid-protein interactions. Recent technical advances in mass spectrometry have allowed unparalled insight into the roles of lipids in neuronal function. Through shotgun lipidomics and multidimensional mass spectrometry, in conjunction with the identification of new classes of phospholipases (e.g., calcium dependent and calcium independent intracellular phospholipases), new roles for lipids in cerebral function have been accrued. This review summarizes the advances in our understanding of the types of lipids and phospholipases in the brain and the role of functional lipidomics in increasing our chemical understanding of complex neuronal processes.

Animals↗

Symposium summary: children's health risk--what's so special about the developing immune system?

In recent years, there has been increasing regulatory pressure to protect the health of children, with the basic tenet being that children differ significantly from adults in their biological or physiological responses to chemical exposures. In a regulatory context, this has been translated to mean a requirement for an additional 10-fold safety factor for environmental contaminants, specialized tests, or both. Much of the initial focus has been on the developing endocrine and nervous systems; but increasingly, the developing immune system has been identified as a potential target organ for chemically mediated toxicity. More recently, the question has been raised regarding whether the current state of science supports the creation of developmental immunotoxicology (DIT) test guidelines. What is needed is a risk-based evaluation of the biology associated with the proposed differential sensitivity between children and adults and the impact of that assessment on additional regulatory measures to protect children in risk assessment analyses. Additionally, an understanding of whether the developing immune system shows greater susceptibility, either qualitatively or quantitatively, to chemical perturbation is critical. To address the question "What's so special about the developing immune system?" a symposium was organized for the 2003 Society of Toxicology annual meeting that brought together risk assessors, clinicians, immunologists, and toxicologists.

Adolescent↗

Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.

Adult↗

Proximo-distal specialization of epithelial transport processes within the Xenopus pronephric kidney tubules.

The embryonic kidneys of larval aquatic vertebrates such as fish and frogs serve as excellent model systems for exploring the early development of nephric organs. These experimental systems can easily be manipulated by microsurgery, microinjection, genetics, or combinations of these approaches. However, little is known about how physiologically similar these simple kidneys are to the more complex mammalian adult kidneys. In addition, almost nothing is known about proximo-distal patterning of nephrons in any organism. In order begin to explore the physiological specialization of the pronephric tubules along the proximo-distal axis, a combination of uptake assays using fluorescently tagged proteins, LDL particles and dextrans, and an informatics-targeted in situ screen for transport proteins have been performed on embryos of the frog, Xenopus laevis. Genes identified to be expressed within unique subdomains of the pronephric tubules include an ABC transporter, two amino acid cotransporters, two sodium bicarbonate cotransporters, a novel sodium glucose cotransporter, a sodium potassium chloride cotransporter (NKCC2), a sodium chloride organic solute cotransporter (ROSIT), and a zinc transporter. A novel combination of colorimetric and fluorescent whole-mount in situ hybridization (FCIS) was used to precisely map the expression domain of each gene within the pronephros. These data indicate specialized physiological function and define multiple novel segments of the pronephric tubules, which contain at least six distinct transport domains. Uptake studies identified functional transport domains and also demonstrated that early glomeral leakage can allow visualization of protein movement into the pronephric tubules and thus establish a system for investigating experimentally induced proteinuria and glomerulonephritis.

Animals↗

Interspecific phylogeography of the Stator limbatus species complex: the geographic context of speciation and specialization.

Diversification in phytophagous insects is often attributed to a propensity toward specialization and to a tendency for speciation to be associated with host-shifts. Phylogenetic analysis revealed a sister relationship between the generalist Stator limbatus and the specialist host-shifted Stator beali, providing a system to examine the genealogical and geographic origins of the main processes involved in this diversification: host-shifts, specialization, and reproductive isolation. We examine the interspecific phylogeographic relationships between these species using mitochondrial DNA sequence data. S. beali is derived within S. limbatus, rendering the latter paraphyletic and suggesting a budding process of speciation. The inherent polarity in this genealogical pattern indicates that the specialist habit, clumping oviposition behavior, and distinct genitalia of S. beali are all derived from the ancestral S. limbatus. The phylogeography of S. limbatus also shows strong geographic structure with divergences corresponding to known biogeographic boundaries, indicating that this evolutionary signal has not been erased by the vagaries of history. However, the derivation of S. beali and the evolution of reproductive isolation between the two species does not correspond to these known biogeographic boundaries, as S. beali and its sister clade of S. limbatus are restricted to the same geographic province. The geographic proximity of diversification combined with a divergence time estimated at the beginning of the Pleistocene indicates that speciation likely occurred very rapidly, although further genetic and ecological work is necessary to examine the mode of speciation. This study provides the historical context for ongoing evolutionary, ecological, and quantitative genetic research on the divergence in diet breadth between these species.

Animals↗

Correlating diet and digestive tract specialization: examples from the lizard family Liolaemidae.

A range of digestive tract specializations were compared among dietary categories in the family Liolaemidae to test the hypothesis that herbivores require greater gut complexity to process plant matter. Additionally, the hypothesis that herbivory favors the evolution of larger body size was tested. Lastly, the association between diet and hindgut nematodes was explored. Herbivorous liolaemids were larger relative to omnivorous and insectivorous congeners and consequently had larger guts. In addition, small intestine length of herbivorous liolaemids was disproportionately longer than that of congeners. Significant interaction effects between diet and body size among organ dimensions indicate that increases in organ size occur to a greater extent in herbivores than other diet categories. For species with plant matter in their guts, there was a significant positive correlation between the percentage of plant matter consumed and small intestine length. Herbivorous liolaemids examined in this study lacked the gross morphological specializations (cecum and colonic valves) found in herbivores in the families Iguanidae and Agamidae. A significantly greater percentage of herbivorous species had nematodes in their gut. Of the species with nematodes, over 95% of herbivores had nematodes only in the hindgut. Prevalence of nematodes in the hindgut of herbivores was 2 x that of omnivores and 4 x that of insectivores.

Adaptation, Biological↗

Screening in special populations: a "case study" of recent Vietnamese immigrants.

PURPOSE: To determine how the medical and social profile of a particular special population, Vietnamese immigrants, should be used to tailor screening protocols that differ from those designed for the general population. PATIENTS AND METHODS: A consecutive series of Vietnamese immigrants living in the United States for less than 6 months were evaluated by interviewer-administered standardized questionnaire and medical record review. A total of 99 new Vietnamese immigrants (47 women and 52 men) aged 19 to 71 years presenting for primary care to two neighborhood health centers between October 1994 and June 1995 were identified. Data collected included smoking status, alcohol use (CAGE questionnaire), depression (Vietnamese Depression Scale [VDS]), PPD status, stool ova and parasites, hepatitis B and syphilis serologies. RESULTS: Overall, 32% were smokers and significantly more men than women smoked (54% vs. 9%) (P < .00001). Although 24% of patients used alcohol, none responded positively to any of the CAGE questions. Using the VDS, 17% (17 of 99) were depressed; age 40 and older was the only sociodemographic factor associated with depression (P < .00001). Ova or parasites were found in 51% (41 of 80), and 63% of those infected (26 of 41) required treatment for pathogenic infections. Seventy percent (66 of 94) tested positive on the tuberculin skin test (PPD), and antituberculous medication was recommended in 39% (37 of 94). Eighty-three percent (80 of 96) had been exposed to hepatitis B, and 14% (13 of 96) were chronic hepatitis B carriers. CONCLUSIONS: Caring for special populations provides an opportunity to institute appropriate unique screening tests not recommended for the general population. In the case of new Vietnamese immigrants, routine screening protocols should include the following: testing for tuberculosis by PPD, stool ova and parasite examinations, hepatitis B serologies, and assessment for depression and smoking status. The CAGE questionnaire may not be an effective instrument for detecting alcohol abuse in this particular population.

Adult↗

Electrical activity in the heart during hyperkalemic hypothermic cardioplegic arrest: site of origin and relationship to specialized conduction tissue.

Previous studies from this laboratory have shown that low-amplitude electrical activity (LEA) may occur during standard hyperkalemic hypothermic cardioplegic arrest and be undetected by routine monitoring techniques. The present study was designed to elucidate the electrophysiological nature of LEA. Ten dogs were monitored continuously during standard cardioplegic arrest using a 32-channel data acquisition system. In 7 animals (Part I), electrophysiological mapping of the lower right atrial septum during arrest was performed. The initial site of activation of LEA was consistently recorded from the region of the lower atrial septum prior to atrial or ventricular electrical activation. The site of origin of LEA was thus localized to the anatomical region of the atrial septum containing the atrioventricular nodal conduction tissue. In Part II, the electrophysiological mechanism of LEA was investigated in the remaining 3 animals utilizing an intrinsic property of specialized conduction tissue. Inclusion of a calcium channel-blocking agent in standard cardioplegic solution completely prevented the development of LEA in all 3 animals, which is in contrast to findings in previous studies using standard cardioplegic solution alone. These data suggest that LEA may be related to calcium-mediated activation of specialized conduction tissue. This mechanism of activation may explain why LEA cannot be detected by the intraoperative monitoring techniques routinely employed.

Animals↗

Measurement and treatment of agitation following traumatic brain injury: II. A survey of the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation.

OBJECTIVE: Determine national patterns of measuring and treating agitation after traumatic brain injury (TBI) by physiatrists with expressed interest in treating TBI survivors. DESIGN: A 70% random sample of members of the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation was surveyed by telephone. MAIN OUTCOME MEASURE: The survey instrument was designed to determine the most common pharmacologic interventions for agitation and, where possible, match each drug with the target behavioral and cognitive characteristics for which it is prescribed. Data were also collected on the manner in which participants measured agitation and judged treatment efficacy. RESULTS: One hundred twenty-nine of 157 responded, yielding an 82% response rate. The majority of respondents were not measuring agitation in a standard fashion. The five most frequently prescribed drugs by the expert stratum were carbamazepine, tricyclic antidepressants (TCAs), trazodone, amantadine, and beta-blockers. In comparison, the nonexperts most often reported prescribing carbamazepine, beta-blockers, haloperidol, TCAs, and benzodiazepines. Desyrel (p = .06) and amantadine (p = .001) were significantly more likely to be chosen by experts than by nonexperts. Experts chose haloperidol significantly less often than nonexperts (p = .01). Prescription of sedating drugs such as haloperidol or benzodiazepines was not found to be associated with the acuity of injury of TBI patients in the respondent's practice, practice setting, or years of practice since completing residency. Choice of haloperidol to treat agitation was not significantly associated with the degree to which explosive anger, verbal aggression, or physical aggression were considered important to the respondent's definition of agitation. CONCLUSIONS: The majority of physiatrists surveyed did not formally measure agitation. Treatment strategies differ significantly between general physiatrists and those who specialize in the treatment of patients with TBI. The breadth of pharmacologic agents and strategies identified in this survey probably reflects the lack of research specific to the pathophysiology of the disorder of posttraumatic agitation.

Adult↗

Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa.

Colonic bacteria release large quantities of the highly toxic thiols hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). These gases rapidly permeate the colonic mucosa, and tissue damage would be expected if the mucosa could not detoxify these compounds rapidly. We previously showed that rat cecal mucosa metabolizes these thiols via conversion to thiosulfate. The purpose of the present study in rats was to determine if this conversion of thiols to thiosulfate is (a) a generalized function of many tissues, or (b) a specialized function of the colonic mucosa. The tissues studied were mucosa from the cecum, right colon, mid-colon, ileum, and stomach; liver; muscle; erythrocytes; and plasma. The metabolic rate was determined by incubating homogenates of the various tissues with H(2)(35)S and CH(3)(35)SH and measuring the rate of incorporation of (35)S into thiosulfate and sulfate. The detoxification activity of H(2)S (expressed as nmol/mg per min) that resulted in thiosulfate production was at least eight times greater for cecal and right colonic mucosa than for the non-colonic tissues. Thiosulfate production from CH(3)SH was at least five times more rapid for cecal and right colonic mucosa than for the non-colonic tissues. We conclude that colonic mucosa possesses a specialized detoxification system that allows this tissue to rapidly metabolize H(2)S and CH(3)SH to thiosulfate. Presumably, this highly developed system protects the colon from what otherwise might be injurious concentrations of H(2)S and CH(3)SH. Defects in this detoxification pathway possibly could play a role in the pathogenesis of various forms of colitis.

Animals↗

Some comments on the special cognitive functions claimed for the hippocampus.

This paper challenges the idea that memory is the special function of any single brain structure, an idea that developed from clinical cases of amnesia that had lesions in and around the hippocampus. There are many instances of amnesia and other evidence of memory functions in brain areas that do not involve the hippocampus. The evidence that medial temporal lobe lesions in animals produce uncontaminated memory deficits is reviewed and rejected, as well as the evidence that the memory task used in these experiments has any special relationship to the hippocampus. It is proposed that memory is not the function of any one structure, but is a part of local neuronal operations carried out in all cortical areas where the information to be remembered is processed and perceived. If this suggestion is correct, then a local lesion will cause a loss of local function and the memory for that function.

Amnesia↗

Right hemisphere specialization for mental rotation in normals and brain damaged subjects.

Hemisphere specialization for mental rotation was investigated utilizing Shepard's (1971) paradigm. In each of two experiments, the procedure involved presenting pairs of novel non-verbal stimuli at various angles of disparity. Subjects were instructed to construct a mental image of one stimulus, rotate this image, and judge whether or not the image was a congruent match with its mate. Both response time and accuracy were measured. In Experiment 1, the testing of right-handed normals revealed a significant left visual field advantage for accuracy (p less than .0001) and response time (p less than .05). In Experiment 2, a comparison of right parietal lesioned patients with both left parietal lesioned patients and matched normal controls likewise revealed significant right lesion effects for accuracy (p greater than .0001) and response time (p greater than .01). Right hemisphere specialization for mental rotation was documented for both normals and brain damaged subjects.

Adolescent↗

Hemispheric specialization for mental rotation.

A sample of 133 normal subjects, and one commissurotomized subject, were given a "mental-rotation" task, in which they were timed as they decided whether rotated letters, flashed in the left or right visual hemifield, were normal or backward. The normal subjects showed a significant right-hemifield advantage in reaction time, while the commissurotomized subject showed a pronounced left-hemifield advantage in both accuracy and reaction time. We argue that mental-rotation is primarily a right-hemispheric specialization, but that this was offset in the normal subjects by a stronger left-hemispheric specialization for letter identification.

Adolescent↗

Specialization of the interphotoreceptor matrices around cone and rod photoreceptor cells in the monkey retina, as revealed by lectin cytochemistry.

The binding sites of two lectins, peanut agglutinin (PNA) and wheat germ agglutinin (WGA), in the interphotoreceptor matrix (IPM) and photoreceptor plasma membranes of the Japanese monkey (Macaca fuscata) retina were localized using a pre-embedding staining method with ferritin-conjugated (Fer) lectins as well as a postembedding staining method with fluorescence-labeled (FITC) lectins. FITC-PNA, but not WGA, stained cylindrical domains of the IPM around cone outer and inner segments, while the IPM around rods stained with FITC-WGA but not PNA. When the intact (not detached) retinal tissues were incubated with Fer-lectin, the lectin generally labeled neither the IPM nor photoreceptor plasma membranes, but labeled only those structures in detached portions occurring at the edges of occasional retinal tissue blocks. Thus, the neural retinas physically isolated from the retinal pigment epithelium (RPE) were utilized principally here. Ultrastructurally, the IPM in the intact retina consisted of granular and filamentous materials; the IPM in the isolated neutral retina also retained those components, although somewhat loosely organized, and the IPM around cones appeared to be preserved better than did the IPM around rods. Fer-PNA bound to the IPM associated with cones, but not rods; Fer-WGA bound to the rod- but not cone-associated IPM. The ferritin particles were found to lie close to the granular and filamentous materials. Those photoreceptor-associated IPMs extended to the apical surface of the RPE in detached portions or to the apical villi of the RPE which were frequently found in the isolated neural retinas. Also, Fer-PNA labeled the cone, but not rod, plasma membranes; Fer-WGA bound heavily to the plasma membranes of rod and cone outer segments, but sparsely to those of their inner segments. These results suggest that the IPM comprises chemically and physically differential domains specialized for cone and rod photoreceptor cells, and that these specialized IPM are structurally so stable that may be involved in isolating photoreceptor cells physicochemically from each other and in the interactions between the photoreceptors and the RPE, such as retinal adhesion.

Animals↗

Survey results on the current practice of ovum donation. Ovum Donor Task Force of the Psychological Special Interests Group of the American Fertility Society.

OBJECTIVE: To investigate how many programs currently have an ovum donor program and to examine the current state of the art in ovum donor programs regarding management, screening, and implementation. DESIGN: Surveys were sent to members of the Society for Assisted Reproductive Technology (SART) and the Psychological Special Interest Group of the American Fertility Society. RESULTS: Of 160 SART members, 82 surveys were returned. Psychological Special Interest Group surveys were excluded. A trend toward more third party reproduction was seen. There was little uniformity among programs regarding medical or psychological screening. Differences were seen between the screening and administration of ovum and sperm donation. CONCLUSIONS: Unlike sperm donation, ovum donation has begun in the known donor realm. Medical and psychological screening is currently limited in many ovum donor programs and highly variable with both known and anonymous donors. Most programs do use a mental health person as part of the screening process. More guidelines are needed to provide uniformity for the current practice of ovum donation.

Age Factors↗

Pediatric home care: an ambulatory "special care unit".

A pediatric home care program is described which has operated as an ambulatory special care unit in an urban hospital center since 1970. The program provides care for seriously or chronically ill children, who would not be adequately served through traditional ambulatory services because of either the severity and complexity of their medical problems or the inability of their families to use such services. An interdisciplinary PHC team provides comprehensive pediatric care and integrates medical and psychosocial services for the child and family. This form of special ambulatory care appears to offer advantages to patients who are at risk in existing ambulatory schemes and is an alternative to inpatient care.

Ambulatory Care↗

Specializations in plasma membranes of the human placenta.

Two distinct plasma membranes have been partially purified and characterized from nomal human placenta. Cell membrane specializations which are likely to interact with maternal blood and humoral agents in the intervillous space were identified on the brush border membrane of the syncytiotrophoblast, which is recognized as the major site of synthetic and transport activity in the human placenta. Another placental plasma membrane fraction, which presumably contains syncytial components and is distinct from brush border membrane, has also been partially characterized. This membrane is likely to be a major site of interaction of fetal blood and humoral agents with the placenta. Both brush border and nonbrush border membranes possess different transport and receptor activities. Brush border membranes are rich in insulin receptors and in alkaline phosphatase and contain Na+-gradient--dependent amino acid transport sites (but do not contain demonstrable hormone sensitive adenylate cyclase activity). Nonbrush border placental membranes are (on the other hand) enriched in hormone sensitive adenylate cyclase activity, beta-Adrenergic receptors, Na+-K+-ATPase, [3H]ouabain binding, and an ATP-dependent Ca2+ transport system. Interposed between two separate circulatory systems the placenta has a distinct polarity of its membrane specializations thus allowing different interactions at the maternal-placental as compared to the fetal-placental interface. These interactions are likely to mediate placental metabolic, synthetic, and transport functions.

Cell Membrane↗