Biomedical subjects

A K Agrawal

Publications and source records attributed to A K Agrawal.

At least 19 recordsLinked to original sources

PubMed2006

Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

In the present study, an attempt has been made to explore the neuroprotective and neuroreparative (neurorescue) effect of black tea extract (BTE) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In the neuroprotective (BTE + 6-OHDA) and neurorescue (6-OHDA + BTE) experiments, the rats were given 1.5% BTE orally prior to and after intrastriatal 6-OHDA lesion respectively. A significant recovery in d-amphetamine induced circling behavior (stereotypy), spontaneous locomotor activity, dopamine (DA)-D2 receptor binding, striatal DA and 3-4 dihydroxy phenyl acetic acid (DOPAC) level, nigral glutathione level, lipid peroxidation, striatal superoxide dismutase and catalase activity, antiapoptotic and proapoptotic protein level was evident in BTE + 6-OHDA and 6-OHDA + BTE groups, as compared to lesioned animals. BTE treatment, either before or after 6-OHDA administration protected the dopaminergic neurons, as evident by significantly higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons, increased TH protein level and TH mRNA expression in substantia nigra. However, the degree of improvement in motor and neurochemical deficits was more prominent in rats receiving BTE before 6-OHDA. Results suggest that BTE exerts both neuroprotective and neurorescue effects against 6-OHDA-induced degeneration of the nigrostriatal dopaminergic system, suggesting that possibly daily intake of BTE may slow down the PD progression as well as delay the onset of neurodegenerative processes in PD.

Animals↗

PubMed2004

Voriconazole-induced musical hallucinations.

1 Voriconazole (Vfend) is a second-generation azole antifungal that is increasing in popularity especially for the treatment of invasive aspergillosis as well as empirically for the febrile neutropenic patient. In addition, voriconazole tends to have a mild side effect profile with reversible visual disturbances being the most widely described effect. We describe a patient who had musical hallucinations secondary to voriconazole. The patient was a 78-year-old man admitted for induction of chemotherapy for acute myelogenous leukemia (AML) who began to have auditory hallucinations, specifically of Christmas music, the 2nd day of voriconazole therapy. His psychiatric evaluation was otherwise unremarkable. After discontinuing voriconazole the hallucinations decreased in intensity by the 2nd day and ceased altogether by the 3rd day. An extensive literature search, including Pfizer drug trial safety data, yielded no other reports of auditory hallucinations with voriconazole. Several other interesting cases of musical hallucinations secondary to a variety of causes have been reported in the literature, and are reviewed. Notably, musical hallucinations tend to occur secondary to temporal lobe insults and often are of a religious or patriotic theme.

Aged↗

PubMed2004

Mosquito repellent (pyrethroid-based) induced dysfunction of blood-brain barrier permeability in developing brain.

Pyrethroid-based mosquito repellents (MR) are commonly used to protect humans against mosquito vector. New born babies and children are often exposed to pyrethroids for long periods by the use of liquid vaporizers. Occupational and experimental studies indicate that pyrethroids can cause clinical, biochemical and neurological changes, and that exposure to pyrethroids during organogenesis and early developmental period is especially harmful. The neurotoxicity caused by MR has aroused concern among public regarding their use. In the present study, the effect of exposure of rat pups during early developmental stages to a pyrethroid-based MR (allethrin, 3.6% w/v, 8h per day through inhalation) on blood-brain barrier (BBB) permeability was investigated. Sodium fluororescein (SF) and Evan's blue (EB) were used as micromolecular and macromolecular tracers, respectively. Exposure during prenatal (gestation days 1-20), postnatal (PND1-30) and perinatal (gestation days 1-20 + PND1-30) periods showed significant increase in the brain uptake index (BUI) of SF by 54% (P < 0.01), 70% (P < 0.01), 79% (P < 0.01), respectively. This increase persisted (68%, P < 0.01) even 1 week after withdrawal of exposure (as assessed on PND37). EB did not exhibit significant change in BBB permeability in any of the group. The results suggest that MR inhalation during early prenatal/postnatal/perinatal life may have adverse effects on infants leading to central nervous system (CNS) abnormalities, if a mechanism operates in humans similar to that in rat pups.

Aging↗

PubMed2004

Restorative potential of dopaminergic grafts in presence of antioxidants in rat model of Parkinson's disease.

Free radical mediated damage has been reported to contribute significantly towards low survival (5-10%) of grafted dopaminergic neurons, post transplantation. In the present study, an attempt has been made to explore the neuroprotective potential of the combination of two major antioxidants ascorbic acid (AA) and glutathione (GSH) on ventral mesencephalic cells (VMC) and nigral dopamine (DA) neurons when co-transplanted together with VMC in rat model of Parkinson's disease (PD). GSH and AA have been reported to act co-operatively in the conditions of oxidative stress thereby helping in maintaining the cellular GSH/GSSG redox status. Functional recovery was assessed 12 weeks post transplantation, where a significant restoration (p<0.001) in d-amphetamine induced circling behavior (62%), spontaneous locomotor activity (SLA; 64%), dopamine-D2 receptor binding (63%), dopamine (65%) and 3,4-dihydroxy phenyl acetic acid (DOPAC) level (64%) was observed in co-transplanted animals as compared to lesioned and VMC alone grafted rats. VMC and GSH+AA co-transplanted animals exhibited a significantly higher surviving TH-immunoreactive (TH-ir) neurons number (p<0.01), TH-ir fibers outgrowth (p<0.05) in striatal graft and TH-ir neurons in substantia nigra pars compacta (SNpc) (p<0.01), as compared to VMC alone transplanted rats. An attempt was made to further confirm our in vivo observations through in vitro experiments where following in vitro exposure to 6-OHDA, a higher cell survival (p<0.01), TH-ir cell counts (p<0.001) and DA and DOPAC levels (p<0.01) were also observed in 8-day-old VMC culture in presence of GSH+AA as compared to VMC cultured in absence of antioxidants. The results suggest that GSH+AA when co-transplanted with VMC provide higher restoration probably by increasing the survival of grafted VMC and simultaneously supporting nigral TH-immunopositive neurons in rat model of PD.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson's disease: a cotransplantation approach with fetal ventral mesencephalic cells.

Different strategies have been worked out to promote survival of transplanted fetal ventral mesencephalic cells (VMCs) using trophic and nontrophic support. Olfactory ensheathing cells (OECs) express high level of growth factors including NGF, bFGF, GDNF, and NT3, which are known to play important role in functional restoration or neurodegeneration. In the present investigation, an attempt has been made to study functional restoration in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) following cotransplantation of VMC and OECs (cultured from olfactory bulb, OB) in striatal region. The functional restoration was assessed using neurobehavioral, neurochemical, and immunohistochemical approach. At 12 weeks, post-transplantation, a significant recovery (P < 0.001) in D-amphetamine induced circling behavior (73%), and spontaneous locomotor activity (SLA, 81%) was evident in cotransplanted animals when compared with 6-OHDA-lesioned animals. A significant restoration (P < 0.001) in [3H]-spiperone binding (77%), dopamine (DA) (82%) and 3,4-dihydroxy phenyl acetic acid (DOPAC) level (75%) was observed in animals cotransplanted with OECs and VMC in comparison to lesioned animals. A significantly high expression and quantification of tyrosine hydroxylase (TH)-positive cells in cotransplanted animals further confirmed the supportive role of OECs in viability of transplanted dopaminergic cells, which in turn may be helping in functional restoration. This was further substantiated by our observation of enhanced TH immunoreactivity and differentiation in VMC cocultured with OECs under in vitro conditions as compared to VMC alone cultures. The results suggest that cotransplantation of OECs and VMC may be a better approach for functional restoration in 6-OHDA-induced rat model of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's disease.

Exogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study the functional restoration following co-transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co-transplanted animals at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA-D(2) receptor binding (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-immunoreactive (IR) fiber density in striatum, as well as TH-IR neurons in substantia nigra pars compacta in co-transplanted animals over VMC-transplanted animals. The result suggests that co-transplantation of CB cells along with VMC provides better and long-term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Behavior of human periodontal ligament cells on CO2 laser irradiated dentinal root surfaces: an in vitro study.

OBJECTIVE: The aim of this study was to investigate the in vitro attachment behavior of human periodontal ligament fibroblasts on periodontally involved root surface after conditioning with CO2 laser and to compare its efficacy with chemical conditioning agents, namely tetracycline hydrochloride, citric acid, hydrogen peroxide (H2O2) and EDTA, using scanning electron microscopy. METHODS: A total of 84 scaled and root-planed specimens from periodontally involved single-rooted human teeth showing hopeless prognosis were selected and assigned to two groups. One group was lased with a CO2 laser (from 5 cm at 3 W for 0.8, 1.0 and 1.2 s), and the other group was treated with either tetracycline hydrochloride (2.5%), citric acid (saturated solution, pH 1), H2O2 (6%) or EDTA (5%; pH 7.4) for 3 min. The specimens were then seeded with human periodontal ligament fibroblasts, incubated for either 12 h or 24 h, and then the cell attachment behavior was observed. RESULTS: CO2 laser irradiation for 1.0 s was found to be the most efficient, showing consistently good cell attachment with the highest mean value (15.00 +/- 3.41 cells/10,000 microm2 after incubation for 12 h and 29.17 +/- 2.04 cells/10,000 microm2 after 24 h), followed by irradiation for 0.8 s (13.11 +/- 3.04 cells/10,000 microm2 after incubation for 12 h and 22.91 +/- 7.10 cells/10,000 microm2 after 24 h). Charring was observed following irradiation for 1.2 s. Amongst chemical conditioning agents, citric acid was found to be the most efficient, with a mean cell attachment of 17.82 +/- 2.16 cells/10,000 microm2 after incubation for 12 h and 23.62 +/- 1.94 cells/10,000 microm2 after 24 h. EDTA and H2O2 did not do well in the study. CONCLUSION: The results suggest that CO2 laser irradiation for 1.0 s may promote comparatively better attachment of periodontal ligament fibroblast on dentinal root surfaces than the conventional chemical conditioning agents used in the study.

Analysis of Variance↗

PubMed2003

Restorative potential of cholinergic rich transplants in cholchicine induced lesioned rats: a comparative study of single and multiple micro-transplantation approach.

Restorative potential of fetal neural transplantation in colchicine induced neurodegeneration was studied in rats; where colchicine (2.5mg per site) was administered bilaterally into the hippocampus followed by bilateral infusions of fetal neural cell suspension rich in cholinergic neurons as single macro- or multiple micro-transplants in the hippocampal region 3 weeks post-colchicine (2.5mg per site) lesion. Animals were studied for neuro behavioural and neurochemical recovery at 4 and 24 weeks post-transplantation and electrophysiological (single cell recording) and immunohistochemical parameters, choline acetyl transferase (ChAT) expression was studied in hippocampus at 24 weeks post-transplantation. Colchicine lesioned rats receiving single macro- or multiple micro-transplants exhibited significant restoration in cognitive dysfunction caused by colchicine after 4 weeks of transplantation which remain persistent in multiple micro-transplanted group upto 24 weeks post-transplantation, whereas, single macro-transplanted animals did not exhibit any significant recovery. Neurochemical studies revealed significant restoration in acetylcholine esterase activity and cholinergic (muscarinic) receptor binding after 24 weeks post-transplantation as compared to 4 weeks post-transplantation in multiple micro-transplanted group. Single cell recording studied at 24 weeks post-transplantation exhibited significant restoration in firing rates when compared with lesioned group. The viability of cholinergic fibre at transplanted sites has further been confirmed by increase in ChAT immuno positivity in hippocampal region using monoclonal antibody and quantified using image analyser Leica Qwin 500 software. The results suggest that intra-hippocampal multiple site cholinergic rich transplants provide better and long term restoration in the cholinergic deficits induced by colchicine lesion as compared to single site macro-transplantation.

Action Potentials↗

PubMed2003

Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation with fetal ventral mesencephalic cells (VMC) on functional restoration in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease: neurobehavioral, neurochemical and immunohistochemical studies.

Among trophic factors already known, glial cell line-derived neurotrophic factor (GDNF) and other members of its family have potent and specific action on dopaminergic neurons. In the present investigation an attempt has been made to validate the role of GDNF co-transplantation with fetal ventral mesencephalic cells (VMC) on functional viability and restoration using neurobehavioral, neurochemical and immunohistochemical parameters at 6 weeks post-transplantation in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). A significant restoration (P<0.01) in D-amphetamine induced rotations, spontaneous and apomorphine induced locomotor activity in rats co-transplanted with VMC and GDNF was observed as compared to VMC alone transplanted rats. Level of dopamine (DA), 3,4-dihydroxy-phenyl acetic acid (DOPAC) and dopamine D2 (DA-D2) receptors in the caudate putamen (CPu) were significantly (P<0.001) restored in co-transplanted group as compared to VMC transplanted or GDNF administered animals. The functional viability of transplanted VMC was confirmed by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-IR fibers density as well as TH-IR neurons counts in co-transplanted animals over VMC transplanted animals. Results suggest that co-transplantation of VMC and GDNF may be a better approach towards functional restoration in 6-OHDA lesioned rat model of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Induced expression of early response genes/oxidative injury in rat pheochromocytoma (PC12) cell line by 6-hydroxydopamine: implication for Parkinson's disease.

The expression of early response gene proteins c-Fos, c-Jun, and GAP-43 and their association with 6-hydroxydopamine (6-OHDA)-mediated oxidative injury were investigated using catecholaminergic PC12 cell line. Significant induction in the expression of c-Fos (P < 0.01), c-Jun (P < 0.001) and GAP-43 (P < 0.05) was observed following 2 h exposure to 6-OHDA (10(-6) M), which persisted during 24 h of observation. The exposed cells exhibited an increase in lipid peroxidation (48, 59 and 33%) along with decreased catalase activity (49, 30 and 13%) and glutathione levels (39, 28 and 16%) following 24, 48 and 72 h exposure, respectively. A concentration-dependent functional impairment of mitochondria as studied by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and decreased cell survival were also observed following 6-OHDA (10(-4), 10(-5) M) exposure for 24, 48 and 72 h. The results indicate a role of the early response gene in oxidative stress-mediated dopaminergic cell death by 6-OHDA. Similar mechanisms may also be operative in the development of Parkinson's disease, as an increased presence/formation of endogenous 6-OHDA has been reported in Parkinson's patients.

Animals↗

PubMed2002

Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain.

In order to examine whether antidepressants mediate their action by interacting with one of the key components of the phosphoinositide (PI) signaling pathway, i.e. PI-specific phospholipase C (PLC), and whether this represents a common mechanism of action of antidepressants, we determined the effects of antidepressants of various classes on PI-PLC activity and on the expression of PLC isozymes in rat brain. It was observed that chronic (21-day) but not acute (1-day) administration with desipramine (DMI), fluoxetine (FLX) and phenelzine (PHLZ), decreased PI-PLC activity in membrane and cytosol fractions of cortex and hippocampus. Similar changes were observed with alprazolam (ALP) and buspirone (BUS), who possess anxiolytic and antidepressant properties. On the other hand, an anxiogenic drug, metachlorophenylpiperazine (MCPP), increased PI-PLC activity in both membrane and cytosol fractions of cortex and hippocampus. The immunolabeling studies showed that all the antidepressants and anxiolytics that caused a decrease in PI-PLC activity also selectively decreased the protein levels of a specific isozyme of PLC, i.e. PLCbeta(1), in membrane and cytosol fractions of cortex and hippocampus, whereas MCPP increased the levels of this particular isozyme. These changes were accompained with changes in the mRNA levels of PLCbeta(1), as determined by quantitative RT-PCR. These antidepressants and anxiolytics did not cause significant changes in the expression of PLC delta(1) or gamma(1) isozyme. Our results thus suggest that modulation of PI-PLC may be common to all classes of antidepressants, which in turn, may be associated with their mechanisms of action.

Animals↗

PubMed2002

The role of dopamine in manganese-induced oxidative injury in rat pheochromocytoma cells.

Reactive dopamine (DA) metabolites have been implicated in both Parkinson's disease and manganese (Mn) neurotoxicity. Rat PC12 and genetically modified PC12 (PC12M) cells capable of producing higher DA content, on exposure to MnCl2 (10(-6) M) for 72 hours, exhibited a significant decrease in glutathione content. Activity of antioxidant enzyme catalase was also inhibited following 24- and 72-hour MnCl2 exposure. MnCl2 caused a concentration-dependent (10(-7) to 10(-3) M) loss in mitochondrial activity after 24 and 72 hours and an impaired DNA synthesis after 72 hours with changes being more marked in PC12M cells. The results indicate that the free-radical-mediated toxicity of Mn at cellular level involves down-regulation of antioxidants in normal and DA-rich PC12 cells. PC12M cells appeared to be more sensitive than PC12 cells.

Animals↗

PubMed2002

Clinical and biochemical profiles of young diabetics in North-Eastern India.

OBJECTIVE: We compared the clinical and biochemical profiles of young diabetics in North Eastern India. METHODS: Seventy diabetics who were detected at less than 30 years of age were studied. Patients with ketoacidosis or ketonuria on insulin withdrawal were grouped as insulin dependent diabetes mellitus (IDDM), patients with history of chronic abdominal pain with or without exocrine pancreatic dysfunction who either on ultrasonography (USG) or endoscopic retrograde cholangiopancreaticoduodenography (ERCP) revealed pancreatic calcification and/or ductal dilatation were grouped as fibrocalculous pancreatic diabetes (FCPD), those having BMI < 19 kg/m2 with history or stigmata of childhood malnutrition and who were ketosis resistant were taken to be protein deficient diabetes mellitus (PDDM)/malnutrition modulated diabetes mellitus (MMDM) and those who neither had ketonuria nor history of chronic abdominal pain, malabsorption or stigmata of malnutrition were grouped as NIDDM of young (NIDDY). RESULTS: Amongst the young diabetics studied FCPD constituted 32.9%, IDDM 28.6%, MMDM 21.4% and NIDDY 17.11%. USG abnormalities were observed in 21 of the 23 patients of FCPD. Seven out of these showed pancreatic head calcification on X-ray while 14 showed pancreatic duct dilatation and calcification or calculi on USG. In the two remaining patients, ERCP revealed tortuousity of main pancreatic duct and calcification which were not detected on USG. Majority of FCPD and MMDM patients revealed insulin resistance on insulin tolerance test (ITT). HDL was significantly lower in NIDDY, while VLDL and triglycerides were significantly higher in FCPD and MMDM as compared to controls. Microvascular complications of diabetes were seen in all these groups, with peripheral neuropathy being more common in FCPD (43.5%) and background diabetic retinopathy in NIDDY (41%). CONCLUSIONS: We conclude that FCPD and MMDM together form majority (54.29%) of young diabetics at our center and a sizeable proportion of them may have microvascular complications, even at the time of diagnosis.

Adolescent↗

PubMed2001

Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose deltamethrin in rats.

Effect of low level in utero exposure to deltamethrin (DT) (1mg /kg wt.) during gestation day 14-20 was studied on selected neurobehavioral, neurochemical, immunohistochemical parameters in rats at 6 and 12 weeks postnatal period. The significant increase in acetylcholinesterase activity and decrease in (3)H-quinuclidinyl benzilate binding in the hippocampal region of DT exposed animals, suggesting impairment in cholinergic (muscarinic) receptors. A significant decrease in the learning and memory performances was also observed both at 6 and 12 weeks, which is directly correlated with decrease in muscarinic receptor binding. Immunohistochemistry and image analysis of growth associated protein-43, a neuron specific protein present in axonal growth cone and a marker for neuronal differentiation and synaptogenesis, exhibit aberrant increase in its expression in the hippocampus in DT exposed rats at both time periods. The data suggests that low level exposure to DT in utero during brain growth spurt period adversely affects the developing brain and the changes persist even up to 12 weeks postnatal period in rats. Although there is no significant recovery at 12 weeks assessment but still significant impairment persist on biochemical and behavioural parameters.

Acetylcholinesterase↗

PubMed2001

Intrinsic signals in the sexually dimorphic circulating growth hormone profiles of the rat.

Male rats secrete growth hormone (GH) in episodic bursts every 3.5-4 h. Between the peaks, GH levels are undetectable. In females, GH secretory profiles are characterized as continuous because hormone concentrations are always measurable in the circulation. These gender differences in the circulating GH profiles are responsible, to varying degrees, for observed sexual dimorphisms ranging from body growth to the expression of hepatic cytochrome P450 (P450, CYP) isoforms. Using hypophysectomized rats in which restored gender-dependent plasma GH profiles were manipulated, we have investigated the importance of the interpulse period in the masculine episodic plasma GH profile in regulating expression (mRNA, protein and/or specific catalytic activity) of male-specific CYP2A2, 2C11, 2C13 and 3A2, female-specific CYP2C12 and female-predominant CYP2A1, 2C6 and 2C7. We observed that some isoforms were induced or suppressed by discerning the length of the GH-devoid interpulse period, others responded to the pulse amplitudes, still others recognized the mean circulating concentrations of GH and some were regulated by a combination of these signals. We conclude that concealed in the gender-dependent circulating GH profiles are numerous intrinsic signals, both inductive and repressive, individually "tailored" to be recognized by each isoform of P450. There would appear to be no one signal in each gender-dependent GH profile responsible, in toto, for the characteristic sexually dimorphic expression of some dozen hepatic P450s in male and female rats.

Animals↗

PubMed2001

Choledochal cyst: a changing pattern of presentation.

BACKGROUND: The aim of the present paper was to study the spectrum of choledochal cysts and analyse the results of various surgical procedures. METHODS: A prospective study was undertaken, at University Hospital, Varanasi, India, of 10 patients with choledochal cyst who presented between January 1996 and June 2000. The patients had a median age at presentation of 16.0 years (interquartile range (IQR): 13.75 years). All patients underwent ultrasonography and endoscopic retrograde cholangiopancreaticography for confirmation of diagnosis. Cyst excision was performed in eight patients followed by reconstruction by hepaticoduodenostomy and Roux-en-Y hepaticojejunostomy in four patients each. Two patients underwent cystoduodenostomy. RESULTS: One patient who underwent hepaticoduodenostomy had a minor leak that responded to conservative management. All patients were asymptomatic at a median follow up of 36.5 months (IQR: 31 months). CONCLUSIONS: There is a changing trend in the commonest mode and age of presentation; fewer patients are presenting with the classical triad and the mean age of presentation is higher. Reconstruction by hepaticoduodenostomy is equally effective, more physiological and less time consuming as compared to hepaticojejunostomy, if the anastomosis can be achieved without tension.

Adolescent↗

PubMed2001

Enhanced immunostimulant activity and protective effect of a synthetic lipopeptide after liposomization against Plasmodium berghei infection in mice.

The immunostimulant activity of non-pyrogenic, sugar-free immunomodulator lipopeptide, Ala-D-Glu(Gly-Lys-CO.C11H23)-NH2 (comp. no 84/201), and its liposomized formulation has been studied. Liposomization of this lipopeptide significantly enhanced its antigen specific as well as nonspecific immune responses, as compared to the free lipopeptide. The liposomized formulation of lipopeptide significantly stimulated both the antibody and delayed-type hypersensitivity responses in Balb/c mice, and also enhanced nonspecifically the macrophage migration index, phagocytic activity and incorporation of 14C glucosamine in peritoneal macrophages of the mice that received pretreatment with this preparation. Further, the mice that received pretreatment with the liposomized preparation strongly resisted lethal P. berghei infection and consequently survived for longer period of times. These results indicate that liposomization of the compound no 84/201 significantly improves its ability to enhance not only antigen-specific immune response but also the nonspecific host's resistance against infections.

Adjuvants, Immunologic↗

PubMed2001

Infusion of gender-dependent plasma growth hormone profiles into intact rats: effects of subcutaneous, intraperitoneal, and intravenous routes of rat and human growth hormone on endogenous circulating growth hormone profiles and expression of sexually dimorphic hepatic cyp isoforms.

The dramatic sexual dimorphism in rat hepatic CYPs is determined by gender differences in the circulating GH profiles. Accordingly, each responsive isoform of CYP is induced or suppressed by different components, i.e., signaling elements, in the GH profiles. It was the purpose of this study to determine whether the signaling elements in the sexually dimorphic plasma GH profiles identified in GH-depleted rats are recognized by the hepatic CYPs in intact rats exposed to a multiplicity of signals contained in the normal gender-dependent GH profiles. To accomplish this goal, we imposed (via osmotic minipumps) the continuous feminine GH profile upon normal male rats and superimposed (via intra-atrial catheters) the episodic masculine profile upon normal females. Monitored circulating GH profiles indicated that the administered GH had little or no effect on the normally secreted gender-dependent endogenous profiles. Basically, we observed that the degree of constancy of GH in the circulation (continuous in females and episodic in males) is the primary determinant establishing sexually dimorphic expression of eight hepatic CYPs in intact rats. However, the characteristic expression levels of each isoform observed in male and female rat liver are determined by an interaction of more subtle signals in the GH profiles reflected in the concentration and persistence of the feminine continuous profile as well as the frequency, duration, and amplitude of pulse and interpulse periods in the masculine episodic profile. In the course of the study, unexpected findings led us to compare the effectiveness of s.c.- and i.p.-infused GH and rGH with hGH. Briefly, male- and female-dependent hepatic CYPs were undoubtedly most responsive to rGH infused by i.p.-implanted osmotic pumps.

Animals↗