Role of Diffusion Tensor Imaging in Early Diagnosis and Characterization of Movement Disorders.

BACKGROUND: Symptoms of movement disorders in early stages are similar, which makes definite diagnosis difficult. Hence this study was conducted to explore the role of diffusion tensor imaging (DTI) in enhancing the early diagnosis and characterization of movement disorders. METHODOLOGY: A cross-sectional study was conducted including 60 subjects. All of them were reviewed using conventional magnetic resonance imaging (MRI) and movement disorder DTI protocol. Commercially available software was used to produce fractional anisotropy (FA) maps. Post-processing 3D reconstruction was done to obtain tractograms. Both single and multiple regions of interest (ROIs) were selected for tractography in the pons, midbrain, substantia nigra (SN) and cerebellum. MRI and DTI images were interpreted and correlated with confirmatory diagnosis. RESULTS: According to DTI diagnosis, out of the 30 cases, 28 had movement disorders. Among cases, 36.67% had Parkinson's disease (PD), 23.33% had progressive supranuclear palsy (PSP), 16.67% had essential tremor, 13.33% had multi-system atrophy (MSA) C, and 3.33% had MSA P. DTI correctly classified all cases with PD and PSP. All cases with long disease duration and 88.24% of cases with short disease duration were also correctly classified. A statistically significant difference was observed in the proportion of diagnosis between DTI and conventional MRI. CONCLUSION: DTI has high sensitivity and specificity for the diagnosis of movement disorders. It is capable of early diagnosis of movement disorders and also differentiating and subcategorizing them.

Exploration of clinical and genetic findings in Ataxia-Telangiectasia (AT) patients from the Indian subcontinent.

BACKGROUND: Ataxia-Telangiectasia (AT) is a rare autosomal recessive neurodegenerative disorder. It is caused by mutations in the Ataxia-Telangiectasia mutated (ATM) gene, which codes for protein ATM serine/threonine kinase. OBJECTIVE: We aim to describe the clinical and radiological findings in children and adolescents of 20 molecularly confirmed cases of AT. We aim to correlate these findings with the genotype identified among them. METHODS: This retrospective study included 20 patients diagnosed clinically and genetically with AT over 10 years. The clinical, radiological and laboratory data were extracted from the hospital's electronic medical records. Molecular testing was done using next generation sequencing and Sanger sequencing. In silico predictions were performed for the variants identified by applying Cryp-Skip, Splice site prediction by Neural Network, Mutation Taster and Hope prediction tool. RESULTS: Consanguinity was documented in nearly half of the patients. Telangiectasia was absent in 10%. Microcephaly was seen in 40% cases. The incidence of malignancy in our study population was low. Molecular testing done in the 18 families (20 patients) identified 23 variants of which ten were novel. Biallelic homozygous variants were noted in 13 families and compound heterozygous in 5 families. Out of the 13 families who were homozygous, 8 families (61.5%) (9 patients) have history of consanguinity. In silico prediction of novel missense variants, NM_000051.4 (ATM_v201): c.2702T > C showed disruption of the α-helix of ATM protein and NM_000051.4 (ATM_v201): c.6679C > G is expected to disturb the rigidity of protein structure in the FAT domain. The four novel splice site variants and two intronic variants result in exon skipping as predicted by Cryp-Skip. CONCLUSIONS: AT should be confirmed by molecular testing in young-onset cerebellar ataxia, even without telangiectasia. Awareness of this rare disease will facilitate study of larger cohorts from Indian population to characterize variants and determine its prevalence in this population.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with vitamin B12 deficiency and adverse perinatal outcomes among pregnant women of rural South India - a cross sectional longitudinal study.

OBJECTIVES: To determine the occurrence of MTHFR gene polymorphisms and to study their association with vitamin B12 deficiency and adverse perinatal outcomes among a cohort of pregnant women from Kaniyambadi block, Tamil Nadu. METHODS: 120 consecutive pregnant women who were ≤20 weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed. RESULTS: Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (χ2)=7.9 and 7.6 respectively; p=0.02]. Heterozygous pathogenic variant c.1262G>T was associated with both adverse maternal [χ2=11.5; p=0.001] and neonatal [χ2=18.3; p=0.009] outcomes. CONCLUSIONS: MTHFR gene polymorphisms could be associated with several adverse perinatal outcomes and vitamin B12 deficiency. Further larger studies are needed to prove the pathogenicity of c.1262G>T variant on pregnancy.

Comparison of Jet Injection Technique with Conventional Injection Technique in Patients Undergoing Endodontic Therapy.

BACKGROUND: In order to reduce the fear and anxiety of injection during root canal procedures, Madajet injection technique was substituted for the first time among the adult patients to obtain its efficacy and to overcome the painful procedure during the conventional syringe technique. AIM: The aim of this study is to compare the clinical efficacy and level of patient acceptance of jet injections with conventional syringe technique in patients with symptomatic pulpitis. METHODOLOGY: Seventy patients were randomly divided into needleless pressure injection technique using Madajet XL and conventional syringe technique. The onset of anesthesia was evaluated using the electric pulp tester, and the pain was assessed using the Visual Analog Scale scoring criteria. STATISTICAL ANALYSIS: The obtained data were tabulated and subjected to the statistical analysis using the Chi-square test. RESULTS: Needleless pressure injection technique (Madajet XL) proves to be effective in patients with symptomatic irreversible pulpitis during endodontic procedure. CONCLUSION: It can be concluded that the needle-less pressure injection technique (Madajet XL) promises to be a viable mode of pain control during endodontic procedures as it converts the solution to a tiny droplet which is then carried by the myelin sheath.

Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study.

INTRODUCTION: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. MATERIALS AND METHODS: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. RESULTS: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2-8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5-10.8) in the definite treatment group and 3.5 years (IQR = 1-5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. CONCLUSION: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.

Simplified chemical processed Cd1-xAlxS thin films for high-performance photodetector applications.

In this present investigation, we report the effect of aluminum (Al) doping on the photoelectric performance of cadmium sulfide (CdS) thin films prepared by cost-effective automatic nebulizer spray method. The doping of Al concentrations varied from 1 at.% to 9 at.% in the steps of 3 at.%. X-ray diffraction (XRD) patterns show hexagonal crystal structure with polycrystalline nature and the enrichment of crystallite sizes as a function of Al doping concentrations. The formed impurity phase i.e. CdO might be helpful in enhancing the photoelectric performance by its additional photo-generated charge carriers. The optical studies confirm the maximum absorption showed in the visible spectral range with the corresponding minimum bandgap of 2.28 eV for 6 at.% of Al. The room temperature photoluminescence studies show an increase of near-band-edge (NBE) emission as a function of Al doping concentration and this NBE is close to the obtained bandgap in terms of wavelength. In addition, the observed red emission at 635 nm is due to the surface-related impurities or native defect states. From the present work, the observed responsivity (R), external quantum efficiency (EQE) and detectivity (D*) of the CdS:Al detectors are 8.64 AW-1, ∼2018% and 9.29 × 1011jones, respectively for the optimum 6 at.% of CdS:Al film. The performance of CdS:Al films reported in this work are significantly improved when compared with literature reports. The present investigation, therefore offers a potential material, CdS:Al, as a photodetector for various scientific and industrial applications.

Lessons from healthcare personnel screening and management during H1N1 pandemic in preparation for the impending COVID-19 pandemic in a tertiary care hospital in India.

BACKGROUND: In the wake of the COVID-19 pandemic caused by a novel corona virus, health care personnel are at increased risk of acquiring the infection. In preparation for the management of health care personnel that are likely to be infected, we looked in to the data collected during the Influenza pandemic in 2009, caused by a novel strain of H1N1 influenza called swine flu. The care of healthcare personnel in our institution, who had an acute febrile respiratory illness (AFRI) during that period was routed through a single channel using a uniform protocol. We retrospectively analysed the available data, during the initial four months of the pandemic, to draw lessons from it. OBJECTIVE: To study the prevalence, clinical profile and risk factors of swine flu among health care personnel during the pandemic of 2009 in a tertiary care hospital in South India. METHODOLOGY: This retrospective study enrolled all the health care personnel including students of a tertiary care institution in South India, who presented with an AFRI between June to August, the initial four months of the swine flu pandemic of 2009. The clinical profile and risk factors were extracted. The results of the RT PCR for swine flu was obtained. Prevalence in each demographic group was calculated and compared. Characteristics of those with swine flu were compared with those who turned negative for the swine flu. RESULTS: The prevalence of all AFRI and only swine flu among health care personnel during the study period was 18 per thousand and 8.7 per thousand respectively. Highest prevalence of swine flu was found among students and office staff. After adjusting for confounding factors, hyperthermia at presentation was significantly higher {OR = 1.97; 95% CI (1.01-3.76)} among those who tested positive for swine flu as compared with those with other AFRI's. Only 2.5% of the entire AFRI group required admission and there was no mortality. CONCLUSION: Health care personnel are at increased risk of acquiring infection. Our study demonstrated that students and office staff were the most susceptible. Unprotected exposure to unknown infectious patients and relatives is likely to have been an important factor. Though the mode of transmission is similar, compared to H1N1, COVID-19 is associated with different comorbidities and has significantly higher mortality. Therefore, in preparation for the COVID-19 pandemic, the personal protective equipment of the healthcare personnel need to be escalated.

Factors influencing the uptake of cervical cancer screening services in Tanzania: A health system perspective from national and district levels.

Aim: This study aimed at examining factors influencing uptake of cervical cancer screening services among women in Tanzania. Design: Exploratory qualitative study. Methods: In-depth interviews were used to obtain information from 10 key Informants. Of these, three were officials (policy makers) from the Reproductive Health-Cancer Unit of Ministry of Health and Community Development, Gender, Elderly and Children (MoHCDGEC), three were health managers working at Kinondoni Municipal health system reproductive and child health section and four were health workers from the Ocean Road Cancer Institute (ORCI). The study participants were purposively selected since they hold the responsibility of planning, coordinating and implementing the Tanzania cervical cancer prevention strategies at different levels of health system. The qualitative data analysis was done manually using thematic analysis. Results: The national health system factors influencing the early uptake of cervical cancer screening services include poor flow of information from national to lower level and inadequate availability of tools and instruments and shortage of skilled and competent staff. The district level health systems factors influencing uptake of cervical cancer screening services include inadequate number of partners, poor flow of information, poor collaboration with the private sector, no adequate provision of cervical cancer screening services due to lack of prioritization, poor creation of awareness and failure to use the health information system effectively.

Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial.

BACKGROUND: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. AIM: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. MATERIALS AND METHODS: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. RESULTS: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. CONCLUSION: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation.

Phenytoin, folic acid and gingival enlargement: Breaking myths.

BACKGROUND: Epilepsy is described as a chronic neurological disorder characterized by recurrent seizures of cerebral origin, presenting with episodes of sensory, motor or autonomic phenomenon with or, without loss of consciousness. A recent meta-analysis of published and unpublished studies puts an overall prevalence rate of epilepsy in India at 5.59 per 1,000 populations. There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the anti-epileptic therapy in the prevention of anti-epileptic drug induced gingival enlargement. However, studies conducted in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy so as to justify the use of folic acid as a routine adjuvant to the usual anti-epileptic therapy to prevent this inevitable adverse effect without destabilizing the ongoing regimen leading to the precipitation of seizures in an otherwise stable patient (breakthrough seizures). MATERIALS AND METHODS: A total of 100 patients between the ages 18 and 50 years were clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was performed prior to the start of and after 1 year of phenytoin therapy. STATISTICAL ANALYSIS USED: The statistical analysis was carried out using t-test and the baseline serum folate levels and the serum folate levels obtained after 1 year of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. RESULTS: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin induced gingival enlargement. CONCLUSIONS: The results of the study suggest a higher incidence of gingival enlargement with an early onset and increased severity in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.

A study on gingival enlargement and folic acid levels in phenytoin-treated epileptic patients: Testing hypotheses.

BACKGROUND: There have been studies that report clinical benefits of the use of folic acid as an adjuvant to the antiepileptic therapy in the prevention of antiepileptic drug-induced gingival enlargement. However, studies in the past have also reported precipitation of epileptic attacks in patients on folic acid adjuvant therapy due to fall in sera levels of phenytoin due to drug interactions. The study was planned to investigate the association of phenytoin-induced gingival enlargement and sera levels of folic acid in epileptic patients on phenytoin therapy. The statistical analysis was done using t-test and the baseline serum folate levels and the serum folate levels obtained after 6 months of phenytoin therapy were correlated with the respective grades of gingival enlargement using Pearson's coefficient formula. METHODS: A total of 25 patients aged between 18 and 50 years, clinically diagnosed with epilepsy prior to the start of phenytoin therapy were included based on selection criteria and written informed consents were obtained. Assessment of serum folic acid levels and gingival enlargement was done prior to the start of and after 6 months of phenytoin therapy. RESULTS: The results of the study confirmed a significant association between low serum folate levels with increasing severity as well as an early onset of phenytoin-induced gingival enlargement. CONCLUSIONS: The results of the study suggest a higher incidence of gingival enlargement in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.

Increased neuronal survival in the brainstem during liver injury: role of γ-aminobutyric acid and serotonin chitosan nanoparticles.

γ-Aminobutyric acid (GABA)- and serotonin (5-HT)-mediated cell signaling, neuronal survival enhancement, and reduced neuronal death in brainstem during liver injury followed by active liver regeneration have a critical role in maintaining routine bodily functions. In the present study, GABAB and 5-HT2A receptor functional regulation, interrelated actions of neuronal survival factors, and expression of apoptotic factors in the brainstem during GABA and 5-HT chitosan nanoparticles-induced active liver regeneration in partially hepatectomized rats were evaluated. Partially hepatectomized rats were treated with the nanoparticles, and receptor assays and confocal microscopic studies of GABAB and 5-HT2A receptors, gene expression studies of GABAB and 5-HT2A receptors, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), Akt-1, phospholipase C, Bax, and caspase-8 were performed with the brainstems of experimental animals. A significant decrease in GABAB and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the brain to trigger the sympathetic innervations during elevated DNA synthesis in the liver. The neuronal apoptosis resulting from the loss of liver function after partial hepatectomy was minimized by nanoparticle treatment in rats compared with rats with no treatment during regeneration. This was confirmed from the gene expression patterns of NF-κB, TNF-α, Akt-1, phospholipase C, Bax, and caspase-8. The present study revealed the potential of GABA and 5-HT chitosan nanoparticles for increasing neuronal survival in the brainstem during liver injury following regeneration, which avoids many neuropsychiatric problems.

The E3 ubiquitin ligase Itch regulates tumor suppressor protein RASSF5/NORE1 stability in an acetylation-dependent manner.

Ras association (RalGDS/AF-6) domain family member RASSF5 is a non-enzymatic RAS effector super family protein, known to be involved in cell growth regulation. Expression of RASSF5 is found to be extinguished by promoter hypermethylation in different human cancers, and its ectopic expression suppresses cell proliferation and tumorigenicity. Interestingly, this role in tumorigenesis has been confounded by the fact that regulation at molecular level remains unclear and many transformed cells actually display elevated RASSF5 expression. Here, we demonstrate that E3 ubiquitin ligase Itch is a unique binding partner of RASSF5. Itch can interact with PPxY motif in RASSF5 both in vivo and in vitro through its WW domains. Importantly, the overexpression of Itch induces RASSF5 degradation by poly-ubiquitination via 26S proteasome pathway. In addition, our results indicate that the elevated levels of RASSF5 found in tumor cells due to acetylation, which restricts its binding to Itch and results in a more stable inert protein. Inhibition of RASSF5 acetylation permits its interaction with Itch and provokes proteasomal degradation. These data suggest that apart from promoter methylation, hyperacetylation could also be downregulating RASSF5 function in different human cancer. Finally, results from functional assays suggest that the overexpression of wild type, not the ligase activity defective Itch negatively regulate RASSF5-mediated G1 phase transition of cell cycle as well as apoptosis, suggesting that Itch alone is sufficient to alter RASSF5 function. Collectively, the present investigation identifies a HECT class E3 ubiquitin ligase Itch as a unique negative regulator of RASSF5, and suggests the possibility that acetylation as a potential therapeutic target for human cancer.

Inflammatory Markers-Serum Level of C-Reactive Protein, Tumor Necrotic Factor-α, and Interleukin-6 as Predictors of Outcome for Peripartum Cardiomyopathy.

AIM/OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a disorder of unknown etiology in which symptoms of heart failure occur between the last month of pregnancy and 5 months post-partum. These findings prompted us to carry out a more detailed study aimed at correlating plasma levels of C-reactive protein TNF-α and IL-6 as prognostic value for major clinical in-hospital events and 6-month follow-up in patients with PPCM. MATERIALS AND METHODS: After ethical clearance, in the present prospective case-control study, a total of 86 subjects were enrolled [patients (n = 46) and controls (n = 40)]. After checking for the inclusion and exclusion criteria, informed consent was obtained and patients were enrolled. The details of history of pre-eclampsia and mode of delivery were obtained from the patients. The history of onset of symptoms and signs was recorded at the first presentation and at 6 months. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. All patients received treatment with diuretics and the ACE inhibitor (ramipril), Carvedilol if not contraindicated, and inotropic support inj-Dobutamine. Inflammatory markers (C-reactive protein, TNF-α, and IL-6) were measured at baseline and at 6 months. Data were analyzed using the SAS version 9.1 statistical program. RESULTS: The characteristics of the study population at first presentation to the cardiac clinic are similar (compared with controls): 0.91 % of the study patients were diagnosed as PPCM patients for the first time and 49 % patients presented within one month after delivery. C-reactive protein (22 vs 08 mg/dl, p < 0.05), TNF-α (9.6 vs 3.2 pg/dl, p < 001), and IL-6 (73.19 ± 34.4 vs 31.52 ± 8.83 pg/dl, p < 0.005) were significantly abnormal, and these patients showed significantly higher LV dimensions, LV EDD (61.6 ± 7.1 vs 46 ± 9 mm p < 0.004) LV ESD (53.1 ± 7 vs 32 ± 8, p < 0.005), and significantly lower echocardiographic left ventricular ejection fraction (LVEF) (25.9 ± 8.2 vs 55 ± 12 p < 0.001) and correlate well with NYHA FC and death. LVEF improved from 25.9 ± 8.2 to 42.9 + 13.6 % at 6 months (p < 0.0001). Patients who completed 6 months of standard care showed a significant reduction of heart rate, LV dimensions, and NYHA FC (p < 0.001). However, normalization of LVEF (>50 %) was only observed in 11 (35 %) patients. Seven patients died within 6 months of diagnoses and eight patients were lost to follow-up. CONCLUSIONS: Plasma markers of inflammation were significantly elevated in PPCM patients and correlated with increased LV dimensions and lower EF at presentation. Baseline CRP, IL-6, TNF-α, and higher NYHA FC were the only predictors of mortality. These results contribute to inflammation which may contribute to the pathogenesis of PPCM and its complications and predictors of mortality.

Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: effect of pyridoxine treatment.

The incidence of type 2 diabetes mellitus is rising at alarming proportions. Central nervous system plays an important part in orchestrating glucose metabolism, with accumulating evidence linking dysregulated central nervous system circuits to the failure of normal glucoregulatory mechanisms. Pyridoxine is a water soluble vitamin and it has important role in brain function. This study aims to evaluate the role of pyridoxine in striatal glucose regulation through dopaminergic receptor expressions in streptozotocin induced diabetic rats. Radio receptor binding assays for dopamine D(1), D(2) receptors were done using [(3)H] 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol and [(3)H] 5-chloro-2-methoxy-4-methylamino-N-[-2-methyl-1-(phenylmethyl)pyrrolidin-3-yl]benzamide. Gene expressions were done using fluorescently labeled Taqman probes of dopamine D(1), D(2) receptor, Insulin receptor, Insulin like growth factor-1(IGF-1) and Glucose transporter-3 (GLUT-3). Bmax of dopamine D(1) receptor is decreased and B(max) of dopamine D(2) was increased in diabetic rats compared to control. Gene expression of dopamine D(1) receptor was down regulated and dopamine D(2) receptor was up regulated in diabetic rats. Our results showed decreased gene expression of Insulin receptor, IGF-1 and increased gene expression of GLUT-3 in diabetic rats compared to control. Pyridoxine treatment restored diabetes induced alterations in dopamine D(1), D(2) receptors, Insulin receptor, IGF-1, GLUT-3 gene expressions in striatum compared to diabetic rats. Insulin treatment reversed dopamine D(1), D(2) receptor, GLUT-3 mRNA expression, D(2) receptor binding parameters in the striatum compared to diabetic group. Our results suggest the potential role of pyridoxine supplementation in ameliorating diabetes mediated dysfunctions in striatal dopaminergic receptor expressions and insulin signaling. Thus pyridoxine has therapeutic significance in diabetes management.

Serum total protein, albumin and advanced oxidation protein products (AOPP)--implications in oral squamous cell carcinoma.

BACKGROUND: The role of oxygen free radicals in the initiation, promotion and progression of carcinogenesis and the protective role of anti-oxidant defenses have been the subject of much speculation in the recent past with conflicting reports in the literature. OBJECTIVES: The aim of this study was to measure the concentration/levels of serum total proteins, albumin and advanced oxidation protein products as markers of oxidative stress in sera of patients with an oral pre-cancerous lesion and frank oral cancer. MATERIALS AND METHODS: The study consisted of sera analysis of 30 new patients of histologically proven well-differentiated, oral squamous cell carcinoma and 10 patients, clinically diagnosed with a potentially malignant epithelial lesion, speckled leukoplakia, aged between 40 to 60 years, in addition to 25 healthy controls. One way analyses of variance were used to test the difference between groups. The normality of data was checked before the statistical analysis was performed. RESULTS: The study revealed variations in sera levels of albumin and advanced oxidation protein products to be statistically significant (p<0.001). CONCLUSION: The results obtained emphasize the need for more studies with larger sample sizes to be conducted before a conclusive role could be drawn in favour of sera levels of total protein, albumin and advanced oxidation protein products as markers of diagnostic significance and of the transition from the various oral pre-cancerous lesions and conditions into frank oral cancers.

A case of acute pancreatitis with occupational exposure to organophosphorus compound.

Pesticides have contributed to dramatic increase in the quality and quantity in crop yields. Organophosphates are commonly used as insecticides in agriculture and are potent toxicants. Patients with organophosphorus poisoning may present with subclinical features of acute pancreatitis. Proper biochemical investigation and clinical correlation helps in diagnosis.

Cerebellar GABA(A) receptor alterations in hypoxic neonatal rats: Role of glucose, oxygen and epinephrine supplementation.

Hypoxia in neonates causes dysfunction of excitatory and inhibitory neurotransmission resulting in permanent brain damage. The present study is to understand the cerebellar GABA(A) receptor alterations and neuroprotective effect of glucose supplementation prior to current sequence of resuscitation - oxygen and epinephrine supplementation in hypoxic neonatal rats. Hypoxic insult caused a significant decrease in GABA(A) receptor number along with down regulated expression of GABA(Aα1,) GABA(Aα5), GABA(Aδ) and GABA(Aγ3) receptor subunits in the cerebellum which accounts for the respiratory inhibition. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GABA(A) receptor subunits expression to near control. Glucose can reduce ATP-depletion-induced alterations in GABA receptors, thereby assisting in overcoming the neuronal damage caused by hypoxia. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations. The reduction in the GABA(A) receptors functional regulation during hypoxia plays an important role in cerebellar damage. Resuscitation with glucose alone and glucose with oxygenation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.

Forensic issues in suicide due to acid ingestion in a case of major depressive disorder.

Although rare, suicide using caustic substances in psychiatric practice is not infrequent. Such circumstances involve important forensic and psychiatric issues. In this case report, death due to sulfuric acid ingestion in a patient with major depressive disorder is reported. The legal issues concerning suicide in a patient with mental illness, autopsy findings, forensic issues, and pathophysiology concerning death by acid ingestion have been discussed.