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Biomedical subjects

N Srivastava

Publications and source records attributed to N Srivastava.

At least 19 recordsLinked to original sources

Behavioral and neurochemical effects induced by pyrethroid-based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period.

Synthetic pyrethroids, besides their use in agriculture, are prevalently used in our houses as mosquito repellent (MR) in the form of aerosol, mats, coils and liquid vaporizers. Inhalation of fumes of the MR/liquid vaporizers may get entry into the brain by breaching the developing blood-brain barrier, hence deleterious to developing nervous system and can lead to long-term functional deficits. In the present study the consequence of MR exposure has further been investigated at various stages of development, evaluating free radical mediated effect pertinent to neurobehavioral and neurochemical functioning. Rat pups were exposed to pyrethroid-based MR (allethrin 3.6% w/v, 8 h/day through inhalation) during prenatal (GD1-20), postnatal (PND1-30) and perinatal (GD1-PND30) period of development and assessments were made on PND31. We observed significant oxidative stress, where an increase in lipid peroxidation and a decrease in antioxidants, glutathione, superoxide dismutase and catalase in various brain areas (cerebellum, corpus striatum, frontal cortex and hippocampus) were evident at all the exposure schedules. The hippocampus was the most affected region and further exhibited altered cholinergic functioning in the form of significant decrease in cholinergic (muscarinic) receptor binding (prenatal 32%, postnatal 35%, perinatal 38%) and inhibition in acetylcholinesterase activity (prenatal 20%, postnatal 31% and perinatal 33%). The neurochemical changes were found to accompany decrease in learning and memory performance in exposed rats, the function governed by hippocampus. The result suggests that pyrethroid-based MR inhalation during early developmental period may have adverse effect on developing nervous system causing cholinergic dysfunction leading to learning and memory deficit.

Acetylcholinesterase↗

Infant and child feeding index.

Traditional indicators of child feeding practices are widely used and appear to be useful, although the validity and reliability of those related to complementary feeding have not been established. Composite child feeding indices have the potential to address some of the methodological constraints related to the quantitative measurement of child feeding practices. They can address the multi-dimensionality of child feeding practices i.e. the need to consider the type, quality, texture, nutrient density of food, frequency of feeding and diversity of the diet; the age-specificity of child feeding practices; and the fact that feeding practices tend to cluster. The main advantage of creating a composite index is that it allows construction of one variable representing various dimensions of feeding or care practices. This variable, in turn, can be used to illustrate graphically the importance of child feeding or care for child outcomes or to model their determinants. This can be invaluable for advocacy, apart from being an indispensable tool for the purposes of research, monitoring and evaluation. Experience with creation of composite child feeding indices with the studies in Accra and DHS data sets from Latin America and Ethiopia has been encouraging and suggests that this is a promising area for future development and program applications.

Child Care↗

Nitrite and malondialdehyde content in cerebrospinal fluid of patients with Parkinson's disease.

Evidence from clinical and experimental studies supports the hypothesis of free radical-mediated damage of dopaminergic neurons in the pathology of Parkin's disease (PD). The present study was undertaken to evaluate the role of nitric oxide and oxidative stress in PD. Estimation of the stable metabolites of nitric oxide (NO, nitrite, nitrate) and malondialdehyde (MDA), an acceptable marker of lipid peroxidation, can provide indirect evidence of involvement of free radicals. Nitrite and malondialdehyde (MDA) levels were estimated in the lumbar cerebrospinal fluid (CSF) of 20 controls and 21 patients with PD. Nitrite and MDA content was not significantly altered in the CSF of PD patients as compared to the controls. Nitrite and MDA levels in CSF of PD patients exhibited no correlation with age, duration of disease, and severity of illness (measured by the Unified Parkinson's Disease Rating Score). There was no correlation between the CSF nitrite and MDA level. Findings of the present study do not provide evidence for the involvement of nitric oxide and oxidative stress in PD.

Female↗

Isotretinoin-induced inflammatory bowel disease.

Three case reports on inflammatory bowel disease associated with use of isotretinoin are described. All three patients were male adolescents, in good health when starting isotretinoin (for acne treatment for about six months). Several weeks after discontinuation of isotretinoin the patients developed severe symptoms requiring hospitalisation. The diagnosis of ulcerative colitis was made in two of these patients, while in the third patient Crohn's disease was diagnosed. Although inflammatory bowel disease is described as an adverse drug reaction in the product information of isotretinoin, few cases have been described so far. The link with prior isotretinoin use may not be recognised by the patient or the physician, since the diagnosis of inflammatory bowel disease is often preceded by several years of vague symptoms. On the other hand, spontaneous onset of inflammatory bowel disease (not related to isotretinoin) cannot be excluded. We appeal to the readers for a reaction to this, to shed more light on the likeliness of this alleged association.

Adolescent↗

An integrated microfluidic device for influenza and other genetic analyses.

An integrated microfluidic device capable of performing a variety of genetic assays has been developed as a step towards building systems for widespread dissemination. The device integrates fluidic and thermal components such as heaters, temperature sensors, and addressable valves to control two nanoliter reactors in series followed by an electrophoretic separation. This combination of components is suitable for a variety of genetic analyses. As an example, we have successfully identified sequence-specific hemagglutinin A subtype for the A/LA/1/87 strain of influenza virus. The device uses a compact design and mass production technologies, making it an attractive platform for a variety of widely disseminated applications.

Animals↗

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↗

Neutrophil-free radical generation and enzymatic antioxidants in migraine patients.

The present study was undertaken to elucidate the role of circulating neutrophils if any in oxidative stress in migraine by evaluating free radical generation and activities of enzymatic antioxidants in the blood in 55 patients with migraine and 60 healthy controls. Free radical generation was assessed by flow cytometry, while activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) was estimated in blood polymorphonuclear neutrophils (PMNs) by standard procedures. Platelet SOD was also measured. No significant change was found in free radical generation and in the activity of catalase, SOD and GPx in migraine patients. Univariate analysis of PMN catalase level revealed that migraineurs with a positive family history had significantly lower catalase activity compared with those with a negative family history. No correlation was found in the activity of antioxidant enzymes with age, duration of disease, time since last attack and headache index. The platelet SOD also did not show any significant change in patients of migraine without aura. Platelet aggregation in the presence or absence of PMNs was also not altered significantly. Thus the findings of the present study suggest that neutrophils are not the cause of oxidative stress observed in migraine patients.

Adult↗

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↗

Cerebrospinal fluid nitrite and malondialdehyde levels in patients with motor neuron disease.

Nitric oxide (NO) mediated oxidative damage may be involved in the pathogenesis of neuronal degeneration in motor neuron disease (MND). The present study was undertaken to evaluate the role of NO and oxidative stress in MND by estimating nitrite and malondialdehyde (MDA) levels in the cerebrospinal fluid (CSF) in 22 patients of MND and 20 control subjects suffering from neurological disorders not known to affect NO metabolism. There was no significant change in the CSF nitrite and MDA levels in MND. The nitrite and MDA levels did not have any significant correlation with age, duration of illness, or severity of disease. Univariate analysis of the clinical features in patients with MND and the nitrite levels revealed that two patients with a positive family history had significantly higher CSF nitrite levels as compared to those with a negative family history. There was no correlation between the CSF nitrite and MDA levels. Results of the present study did not indicate significant alterations in the MDA and NO levels in the CSF of MND patients. However, involvement of NO in MND with positive family history is suggested by the results obtained.

Adult↗

Fused supernumeraries in deciduous dentition: a case report.

The occurrence of supernumerary teeth and fusion of two teeth is not a very rare findings but the fusion of two supernumeraries especially in primary is very rare. Reported here, is a case of three supernumerary teeth present in the same region, out of which two of them were fused with each other. Since the interference with the normal eruption of the permanent successor was anticipated, the fused supernumeraries were extracted.

Child, Preschool↗

A study on nitric oxide, beta-adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression.

BACKGROUND: alterations in the polymorphonuclear leukocyte (PMNs) receptors, second messenger system and in their responses have been found associated with depression. Recently role of tetrahydrobiopterin and nitric oxide has also been reported in the depressive disorders. It was therefore considered worthwhile to investigate the NOS activity in the PMNs, which like neurons, also express neuronal NOS (nNOS), antioxidant enzyme levels [superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx)] and beta-adrenergic receptors in the patients of depression. METHODS: patients were diagnosed according to the DSM-IV and were medication free, while healthy age-matched controls were also included in the study to estimate nitrite content, beta-adrenergic receptors and antioxidant enzymes in the PMNs according to the standard methodologies. RESULTS: an analysis of 66 cases of depression and 114 controls revealed 73% decrease in nitrite content and 71% decrease in beta-adrenergic receptor binding in the patients as compared to the healthy controls. However, activities of SOD, catalase and Gpx were not significantly altered in the patients. CONCLUSION: the results of the present study for the first time indicate alterations the NOS activity in PMNs obtained form the patients of affective disorders.

Adolescent↗

Differential V gene expression detected in the immune response to Streptococcus pneumoniae capsular polysaccharide between elderly and young adults.

Streptococcus pneumoniae is one of the major causative agents of respiratory infections in the elderly population. The 23-valent pneumococcal polysaccharide vaccine is recommended for use in this age group. However, research has indicated that the protective efficacy of the vaccine declines with age. Although similar levels of antibody induction are seen in both young and elderly adults, following immunization with this vaccine, recent studies have indicated that the elderly possess antibodies with lower opsonophagocytic activity and avidity than young adults. We investigated whether a shift in V(H) gene usage may be responsible for this observation. To this end we utilized anti-idiotypic determinants to detect V(H)1 and V(H)3 gene usage by antibodies to pneumococcal capsular polysaccharides in both young and elderly subjects by enzyme-linked immunosorbent assay (ELISA). We found no significant difference in V(H)3 idiotypic expression in antibody responses to capsular polysaccharide from serotype 14 (PPS14). In response to PPS14 a significant higher level of V(H)1 idiotypic expressing antibodies was detected in the elderly as compared with young adults. V(H)1 idiotypic expression in response to capsular polysaccharide from serotype 4 (PPS4) was identical in young and elderly individuals. V(H)3 idiotypic expression in the elderly response to PPS4 was significantly lower than that seen in young individuals. These patterns of idiotypic expression are discussed in relation to recent studies of functional activity of pneumococcal reactive antibodies from young and aged humans.

Adult↗

Evaluation of the immunocontraceptive potential of Escherichia coli-expressed recombinant dog ZP2 and ZP3 in a homologous animal model.

Dog zona pellucida glycoprotein 2 (dZP2), excluding the N-terminal signal sequence and the C-terminal transmembrane-like domain, was cloned and expressed as a polyhistidine fusion protein in Escherichia coli to evaluate the immunocontraceptive efficacy of ZP glycoproteins. The recombinant dZP2 (rec-dZP2) revealed a 70 kDa band corresponding to the full length transcript, as well as several low molecular mass fragments in western blot analysis. In addition to rec-dZP2, E. coli expressed recombinant dog ZP glycoprotein 3 (rec-dZP3), which has also been evaluated for its efficacy to block fertility in a homologous system. Three groups of female dogs (n = 4 per group) were immunized with rec-dZP2 conjugated to diphtheria toxoid (rec-dZP2-DT), rec-dZP3 conjugated to DT (rec-dZP3-DT) and DT alone. Immunization of female dogs with rec-dZP2-DT and rec-dZP3-DT led to generation of antibodies against the respective ZP proteins as well as to DT. Subsequent to mating, the four female dogs immunized with rec-dZP2-DT all conceived, which is indicative of failure of the anti-rec-dZP2 antibodies to block fertility. In the group of dogs immunized with rec-dZP3-DT, three of four animals did not conceive when mated with males of proven fertility. The block in fertility was associated with anti-dZP3 antibody titres. Ovarian histopathology revealed that the block in fertility in the group immunized with rec-dZP3-DT is probably manifested by inhibition in the development of follicles and is due to atretic changes in the zona pellucida. These results, although preliminary, indicate that immunization with dZP3 may be a feasible proposition to control dog populations provided that adequate antibody titres are achieved.

Animals↗

ProJuvant (Pluronic F127/chitosan) enhances the immune response to intranasally administered tetanus toxoid.

The potential to generate both a systemic and local immune response makes the mucosal system an attractive site for immunization. However, mucosal administration of protein and peptide antigens generally results in a poor immune response. Successful mucosal vaccination is therefore largely dependent on the development of effective mucosal adjuvants. In this study we have examined the effect of mucosal administration of tetanus toxoid (TT) in the presence of a non-ionic block copolymer, Pluronic F127 (F127), with chitosan or lysophosphatidylcholine (LPC) on the systemic and mucosal immune response. Balb/c mice, immunized intraperitoneally (i.p.) with TT and boosted intranasally (i.n.) with TT in F127/chitosan, demonstrated a significant enhancement in the systemic anti-TT antibody response compared to mice boosted i.n. with TT in PBS or mice boosted i.n. with TT in F127/LPC. We determined the antigen specific IgA response in the nasal and lung washes of these animals and found a significant increase in anti-TT mucosal IgA response in the group boosted with TT in F127/chitosan. Similarly, mice immunized and boosted i.n. with TT in F127/chitosan had a significant enhancement of their systemic anti-TT IgG and mucosal IgA antibody responses compared to the animals immunized and boosted i.n. with TT in PBS or TT in F127/LPC. The results of these studies suggest that F127/chitosan represents a novel mucosal vaccine delivery system, consisting of two components, that appear to exert an additive or synergistic effect on the immune response.

Adjuvants, Immunologic↗

Effects of age and GDNF on noradrenergic innervation of the hippocampal formation: studies from intraocular grafts.

Recent studies have suggested that factors in the target tissue influence the degree of plasticity and regeneration following aging and/or specific insults. We have investigated whether young or aged targets differ in their noradrenergic innervation from fetal locus coeruleus (LC) neurons, and also if a specific growth factor, glial cell line-derived neurotrophic factor (GDNF) can affect this innervation pattern. Tissue pieces of fetal brainstem and young (3 months) or old (18 months) iris tissue were transplanted simultaneously into the anterior chamber of the eye of adult hosts. We found that aged iris transplants became innervated to a significantly lesser degree by the cografted LC neurons than young iris transplants. Fetal hippocampal tissue was then grafted to adult hosts, and a fetal brainstem graft containing LC neurons was placed adjacent to the first graft, either at 3 or 21 months post-grafting. Thus, old/young chimeras of the noradrenergic coeruleo-hippocampal pathway were created. Aged hippocampal grafts received a much less dense innervation from co-grafted LC neurons than young hippocampal grafts. Tyrosine hydroxylase-positive-immunoreactive innervation was only found in the outskirts of aged grafts, while the young hippocampal grafts contained an even innervation pattern. The innervation density of hippocampal grafts was significantly enhanced by GDNF treatment. These findings demonstrate that target-derived factors may regulate neuronal plasticity, and that the age of the target is more important for innervation properties than the age of the neuron innervating a particular target.

Aging↗

A DNA vaccine encoding a peptide mimic of Streptococcus pneumoniae serotype 4 capsular polysaccharide induces specific anti-carbohydrate antibodies in Balb/c mice.

Streptococcus pneumoniae is a leading cause of morbidity and mortality in both the developing and developed world. The T-independent nature of the current polysaccharide vaccine renders it ineffective in elderly adults and children <2 years of age. Although the recently licensed conjugate vaccines are capable of producing T-cell-dependent immunity, they also have their limitations, namely a lack of response in certain populations. Our laboratory has focused on a different approach, DNA vaccination. We have defined a peptide sequence (pep4) that mimics the S. pneumoniae serotype 4 capsular polysaccharide (PPS4) using a monoclonal antibody to PPS4 (mAb4) and phage display library. Pep4 was synthesized, complexed to proteosomes and used to immunize mice. We have shown by ELISA that this peptide mimic is capable of eliciting an anti-PPS4 immune response significantly higher than in negative control mice (P<0.05). A PPS4-DNA vaccine was made by cloning an oligodeoxynucleotide encoding pep4 into the HBcAg vector. Following epidermal immunization with the PPS4-DNA vaccine, mice produced an anti-PPS4 antibody response significantly higher than in mice immunized with an impertinent DNA vector (P<0.05). Our results demonstrate the feasibility of peptide mimicry in DNA vaccine development.

Amino Acid Sequence↗

Nitrite content and antioxidant enzyme levels in the blood of schizophrenia patients.

RATIONALE: Recent studies have suggested augmentation in the inflammatory response as well as involvement of nitric oxide (NO) in mood disorders. Polymorphonuclear leukocytes (PMN), NO and free radicals have been associated with inflammatory response; however, the status of NO in the PMN has not been investigated so far in schizophrenia patients. OBJECTIVES: The present study was undertaken to investigate levels of nitrite (a metabolite of NO), malonaldehyde (MDA, lipid peroxidation product) and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx) in the PMN of schizophrenia patients. METHODS: Patients with schizophrenia (n=62) were diagnosed according to DSM-IV and were free of anti-psychotic medications/ECT for at least 3 months. Mean age of the patients was 29.06+/-1.17 years, with a male to female ratio of 4:1, and mean duration of illness was 3.7+/-0.6 years. The control group consisted of 82 healthy subjects with a mean age of 37.0+/-1.26 and a male to female ratio of 5:1. PMN were isolated from the blood. Nitrite, MDA and antioxidant enzymes were estimated by standard biochemical techniques in the PMN of normal healthy controls and schizophrenia patients. Platelet and plasma nitrite levels were also estimated in controls and schizophrenia patients. RESULTS: Nitrite content in the PMN was reduced to 68%, while plasma and platelet nitrite content in schizophrenia patients was not significantly changed in comparison to controls. Malonaldehyde (MDA) content in PMN was significantly augmented in schizophrenia patients but activity of SOD, catalase and Gpx remain unaltered. CONCLUSION: Results obtained indicate a significant decrease in NO synthesis and an increase in MDA in the PMN of schizophrenia patients, while antioxidant enzyme activities were not altered in the PMN of schizophrenia patients. This suggests that the decrease in PMN NO synthesis by PMN might lead to oxidative stress in schizophrenia patients.

Adolescent↗

Dietary cholate increases plasma levels of apolipoprotein B in mice by posttranscriptional mechanisms.

To induce atherogenesis in mice, a high fat (HF) diet is supplemented with cholic acid (CA), which increases apoB-containing particles and lower apoA-I-containing particles. HF diet without CA increases levels of both HDL and LDL, suggesting that CA may be responsible for the elevation of LDL and lowering of HDL. The mechanism of dietary CA-induced lowering of apoA-I-containing particles has recently been reported. In this study, we examined the mechanism of CA- and HF-induced elevation of apoB-containing lipoproteins in mice. Mice were fed the following four diets: control chow (C), high fat high cholesterol, (HF), control and 0.5% cholate (CA), and HF+CA. Dietary CA increased the plasma levels of apoB-containing particles by approximately 2-fold when compared to control; VLDL levels increased 2-fold, and LDL levels increased 1.3-fold. On HF diet, VLDL increased by 1.4-fold, and LDL by 2-fold, suggesting that CA and HF-induced increases of apoB-containing particles occurred by different mechanisms. We investigated the potential mechanisms regulating plasma levels of apoB in CA- and HF-fed mice. Although hepatic apoB mRNA levels did not change on CA diet, apoB-100 mRNA increased relative to B-48 as a result of decreased editing of apoB mRNA. Measurements of hepatic LDL receptor mRNA suggested that CA diet down-regulated LDL receptor mRNA, possibly by increasing the levels of hepatic cholesterol. Since plasma and hepatic vitamin E levels did not show significant changes on CA-containing diets, it suggests that dietary CA did not act by increasing the absorption of dietary fat. Hepatic lipase, known to modulate plasma levels of apoB-containing particles, did not show changes in CA- or HF-fed mice. Taken together, these results suggest that dietary CA increased apoB-containing particles both in chow-fed and fat-fed mice by enhancing the relative production of apoB-100, and also by reducing LDL receptor-mediated clearance of apoB-containing particles. Thus, dietary cholate modulates plasma levels of apoB primarily by posttranscriptional mechanisms.

Animals↗