Study on Factors Associated with Depression among Elderly and Comparison of Two Scales Used for Screening.

BACKGROUND: Depression is one of the most frequent illnesses found among the elderly. ICD-10 scale and Geriatric Depression Scale (GDS) are used commonly for screening and hence it is important to identify the scale which can be used more effectively in community settings. OBJECTIVES: (1) To analyze the factors responsible for the elderly depression and (2) to compare two scales used for the screening (ICD-10 and GDS). MATERIALS AND METHODS: A cross-sectional house-to-house survey was carried in Sayla taluka of Surendranagar district by directly questioning the subjects after oral and written consent. The selection of taluka was done using simple random sampling and sample size was calculated on the basis of estimated geriatric population. 306 subjects were interviewed using a predesigned, pretested, and validated questionnaire. RESULTS: GDS showed the prevalence of 16% whereas ICD-10 showed 22%. The factors associated with depression were physical health, poor economical situation, and avoidance by family members. The agreement between the 2 scales using Cohen's kappa statistic showed excellent agreement. CONCLUSION: Community-based multiphasic screening programs is needed for early diagnosis of geriatric depression. ICD-10 having lesser number of questions can be used in the 1st phase of screening and those found positive can then be tested by GDS.

Drug-drug interactions in pharmacologic management of gastroparesis.

BACKGROUND: Gastroparesis is a disorder characterized by delayed gastric emptying due to chronic abnormal gastric motility. The treatment of the disease often entails the co-administration of several classes of pharmacological agents. These agents may be metabolized via the same pathway. Inhibition or induction of a shared metabolic pathway leads to change in the systemic levels of prescribed drugs, possibly leading to undesired clinical outcomes. PURPOSE: This review discusses different pharmacological treatment for gastroparesis patients and describes the potential for drug-drug interactions (DDIs) in some of the combinations that are currently used. Prokinetic agents such as metoclopramide and domperidone are the cornerstone in treatment of gastroparesis. Antiemetic agents such as promethazine and ondansetron are frequently administered to gastroparesis patients to reduce nausea and vomiting. Gastroparesis is prevalent in diabetic patients and therefore antidiabetic agents are also prescribed. Many of these co-administered drugs are metabolized via common drug metabolizing enzymes and this can trigger potential DDIs. The scientific literature was reviewed from the years 1975-2014 for original research articles and reviews that evaluated DDIs in gastroparesis. Many commonly prescribed combinations were predicted to cause potential DDIs in gastroparesis patients. This review will help inform about potential hazardous combinations. This information will hopefully lead to less adverse effects and more successful gastroparesis management.

ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans.

This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational interpretation of transporter-knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter-mediated pharmacokinetics and drug-drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science.

Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.

Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.

Ceruloplasmin alters intracellular iron regulated proteins and pathways: ferritin, transferrin receptor, glutamate and hypoxia-inducible factor-1α.

Ceruloplasmin (Cp) is a ferroxidase important to the regulation of both systemic and intracellular iron levels. Cp has a critical role in iron metabolism in the brain and retina as shown in patients with aceruloplasminemia and in Cp-/-hep-/y mice where iron accumulates and neural and retinal degeneration ensue. We have previously shown that cultured lens epithelial cells (LEC) secrete Cp. The purpose of the current study was to determine if cultured retinal pigmented epithelial cells (RPE) also secrete Cp. In addition, the effects of exogenously added Cp on iron regulated proteins and pathways, ferritin, transferrin receptor, glutamate secretion and levels of hypoxia-inducible factor-1α in the nucleus were determined. Like LEC, RPE secrete Cp. Cp was found diffusely distributed within both cultured LEC and RPE, but the cell membranes had more intense staining. Exogenously added Cp caused an increase in ferritin levels in both cell types and increased secretion of glutamate. The Cp-induced increase in glutamate secretion was inhibited by both the aconitase inhibitor oxalomalic acid as well as iron chelators. As predicted by the canonical view of the iron regulatory protein (IRP) as the predominant controller of cellular iron status these results indicate that there is an increase in available iron (called the labile iron pool (LIP)) in the cytoplasm. However, both transferrin receptor (TfR) and nuclear levels of HIF-1α were increased and these results point to a decrease in available iron. Such confounding results have been found in other systems and indicate that there is a much more complex regulation of intracellularly available iron (LIP) and its downstream effects on cell metabolism. Importantly, the Cp increased production and secretion of the neurotransmitter, glutamate, is a substantive finding of clinical relevance because of the neural and retinal degeneration found in aceruloplasminemia patients. This finding and Cp-induced nuclear translocation of the hypoxia-inducible factor-1 (HIF1) subunit HIF-1α adds novel information to the list of critical pathways impacted by Cp.

What do we (not) know about how paracetamol (acetaminophen) works?

WHAT IS KNOWN AND BACKGROUND: Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. OBJECTIVE: To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. METHODS: A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. RESULTS: Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. WHAT IS NEW AND CONCLUSION: Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts.

Cytochrome P450 CYP2C19 genotypes in Nigerian sickle-cell disease patients and normal controls.

BACKGROUND AND OBJECTIVE: Subjects with different CYP2C19 genotypes may metabolize proguanil, a pro-drug used for malaria prophylaxis differently and the frequency of the different alleles may be different in patients with sickle-cell disease (SCD) and normal controls. The objective of this study was to evaluate CYP2C19 *1, *2 and *3 allele and genotype frequencies in Nigerian normal controls and SCD patients, and to further compare variant CYP2C19 frequencies in Nigerians with other African populations. METHODS: Genotyping was carried out with PCR and restriction fragment length polymorphism analysis. RESULTS AND DISCUSSION: CYP2C19 *1 (84·3 vs. 84·9%) or *2 allele frequency (15·7 vs. 15·1%) was not significantly different between patients with SCD and normal subjects. No *3 allele was detected in the cohort. The SCD group exhibited a statistically significantly lower frequency of *1/*1 genotype (69·6%) compared with normal controls (74·4%). Frequency of *2/*2 was significantly lower in SCD (0·9%) compared with normal controls (4·7%). Frequencies of *1/*2 (29·6 vs. 20·9%) were no different in SCD and normal controls. CONCLUSION: Prevalence of CYP2C19 polymorphisms was defined for the first time in Nigerian normal and SCD populations. Nigerian SCD patients exhibited significantly lower CYP2C19 *1/*1 and *2/*2 frequencies than normal controls. No differences were detected in CYP2C19 allele or genotype frequencies in normal subjects between this study and previous reports in other African populations.

Variability of NS1 proteins among H9N2 avian influenza viruses isolated in Israel during 2000-2009.

The main aims of the present study were to characterize NS1 protein from H9N2 avian influenza viruses (AIVs) isolated in Israel and to investigate the possibility to use NS1-based indirect ELISA. To achieve these purposes, the non-structural gene (NS1) of 79 AIVs of the H9N2 subtype isolated in Israel in 2000-2009 was sequenced and genetically analyzed. The phylogenetic analysis demonstrated that four distinct introductions of H9N2 occurred in Israel during this period. Analysis of the inferred amino acid sequences of the NS1 proteins showed high, about 10%, differences between viruses of the 3rd and 4th introductions. Antibodies against NS1 protein in immune sera were tested by means of indirect ELISA using recombinant NS1 as antigen. Immune sera were obtained from experimentally H9N2-infected chicken after infection on 4, 7, 10, 14, and 21 days. All sera from chickens experimentally infected with 3rd- or 4th-introduction AIV contained anti-NS1 antibodies that were detected by enzyme-linked immunosorbent assay (NS1-ELISA) even though the recombinant NS1 used as antigen for NS1-ELISA differed significantly in its amino acid sequences from the NS1 protein of AIV that caused infection in experimental birds. These findings indicate that the sites of the NS1 protein by which viruses belonging to 3rd and 4th introduction are out of antigenic epitope positions were responsible for the results of NS1-based iELISA.

Avian influenza virus H9N2 survival at different temperatures and pHs.

The H9N2 avian influenza virus (AIV) subtype has become endemic in Israel since its introduction in 2000. The disease has been economically damaging to the commercial poultry industry, in part because of the synergistic pathology of coinfection with other viral and/or bacterial pathogens. Avian influenza virus viability in the environment depends on the cumulative effects of chemical and physical factors, such as humidity, temperature, pH, salinity, and organic compounds, as well as differences in the virus itself. We sought to analyze the viability of AIV H9N2 strains at three temperatures (37, 20, and 4 C) and at 2 pHs (5.0 and 7.0). Our findings indicated that at 37 C AIV H9N2 isolate 1525 (subgroup IV) survived for a period of time 18 times shorter at 20 C, and 70 times shorter period at 4 C, as measured by a decrease in titer. In addition, the virus was sensitive to a lower pH (pH 5.0) with no detectable virus after 1 wk incubation at 20 C as compared to virus at pH 7.0, which was viable for at least 3 wk at that temperature. The temperature sensitivity of the virus corresponds to the occurrence of H9N2 outbreaks during the winter, and lower pH can greatly affect the viability of the virus.

Cis-resveratrol glucuronidation kinetics in human and recombinant UGT1A sources.

It was hypothesized that cis-resveratrol glucuronidation contributes to a greater extent to in-vitro disposition of total resveratrol than previously assumed. To this end, the kinetic data for cis-resveratrol glucuronidation are reported. Glucuronidation assays were conducted in human liver and intestinal microsomes and in uridine diphosphate-glucuronosyltransferases (UGTs) UGT1A1, UGT1A6, UGT1A9, and UGT1A10. Kinetic parameters were estimated for the major cis-resveratrol-3-O-glucuronide (cis-R3G). Substrate inhibition was observed with apparent V(max), K(m) and K(i) of 6.1 +/- 0.3/27.2 +/- 1.2 nmol min(-1) mg(-1), 415 +/- 48.1/989.9 +/- 92.8 and 789.6 +/- 76.3/1012 +/- 55.9 microM in human intestinal microsomes (HIMs) and UGT1A6, respectively (estimate +/- standard error (SE)). Biphasic kinetics were observed in human liver microsomes (HLMs), while sigmoidal kinetics were seen in UGT1A9 (V(max) = 11.92 +/- 0.2 nmol min(-1) mg(-1); K(m) = 360 microM; n = 1.27 +/- 0.07). The 4'-O-glucuronide (cis-R4'G) exhibited atypical kinetics in HLM, HIM, UGT1A1, and UGT1A10. UGT1A9 catalysed cis-R4'G formation at high substrate concentrations (V(max) = 0.33 +/- 0.015 nmol min(-1) mg(-1); K(m) = 537.8 +/- 67.8 microM). In conclusion, although the rates of formation of cis-R3G in HLM and UGT1A9 were higher than those for trans-R3G, the contribution to total resveratrol disposition could not be determined fully due to atypical kinetics observed.

Distribution of ferritin chains in canine lenses with and without age-related nuclear cataracts.

PURPOSE: It was determined in an earlier study that ferritin-heavy (H) and -light (L) chains in lens fiber cells are modified in comparison to those in lens epithelial cells. The purpose of the present study was to determine whether changes in ferritin chain characteristics are developmental, age-related, or associated with cataractogenesis, by analyzing the distribution of modified chains throughout the lens fiber mass. METHODS: After removing the capsule, noncataractous and cataractous lenses were separated into six layers of fiber cells. The content of ferritin H and L chains in each layer was determined by western blotting with chain-specific antibodies. The level of ferritin complex (450 kDa protein made up of assembled L and H chains) was determined using the enzyme-linked immunosorbent assay. The ability of ferritin complex to bind iron was assessed by in vitro labeling with (59)Fe. RESULTS: Fiber cell ferritin L chains were 30 kDa (modified from the normal 19 kDa), and were present at the highest level in the outermost layers of both cataractous and non-cataractous lenses. The amount of modified L chains decreased gradually in the inner layers of the fiber mass, and was undetectable in the inner two layers of cataractous lenses. The ferritin H chains were also modified to 12 kDa (perhaps truncated from the normal 21 kDa size) in both cataractous and non-cataractous lenses. Similar levels of this modified H chain were found throughout the normal lens. Interestingly, in cataractous lenses, the modified H chains were found in decreasing amounts towards the interior of the lens, and were undetectable in the nucleus. However, in these cataractous lenses, the normal-sized ferritin H chains (21 kDA) appear in small quantities in the outer fiber layers, and increase in quantity and size (to 29 kDa) in the inner layers. This observation was best seen and demonstrated in advanced cataracts. Ferritin, which can bind iron, was found mainly in the outer layers of the lens fiber mass of normal lenses, but was more evenly distributed in fiber layers from cataractous lenses. CONCLUSIONS: Both ferritin H and L chains were modified in lens fiber cells from normal and cataractous canine lenses. These modifications were not age-related, and most likely occur during the differentiation of epithelial cells to fiber cells, since only normal-sized chains have been found in lens epithelial cells. In addition, there was a specific and distinct distribution of these modified chains throughout the lens fiber mass. The most striking differences between normal and cataractous lenses fiber cells were the appearance of normal-sized ferritin H chains and the relatively even distribution of iron binding capacity throughout the fiber mass of the cataractous lenses. These differences may reflect a response of the lens to increased oxidative stress during cataractogenesis.

Critical review of ropinirole and pramipexole - putative dopamine D(3)-receptor selective agonists - for the treatment of RLS.

Ropinirole hydrochloride (REQUIP, ADARTREL) and pramipexole dihydrochloride (MIRAPEX, SIFROL) are two putative dopamine D(3) receptor subtype-selective agonists recently approved by the FDA for the treatment of 'restless legs syndrome' (RLS). RLS is a difficult to define condition that is possibly more prevalent than previously thought. Direct-to-consumer advertising has raised public and professional awareness of RLS, but questions, even skepticism about the very existence of the condition, persist. The drugs have adverse effects that can negatively impact on quality of life and thus, as true for all drugs, require consideration of the benefit : risk ratio. We review the definition, diagnostic criteria, pathophysiology, and treatment of RLS, and assess the clinical and preclinical evidence for a pharmacologic rationale for D(3) agonism in general and of the claimed D(3) selectivity of ropinirole and pramipexole in particular.

Metabolic interactions between prokinetic agents domperidone and erythromycin: an in vitro analysis.

This study examined in vitro interaction between domperidone and erythromycin. Both are prescribed for refractory gastroparesis. Domperidone is metabolized via human cytochrome P4503A4. Erythromycin is a CYP3A4 inhibitor. Incubations evaluated domperidone metabolite formation in human liver microsomes and recombinant CYP3A4. Concentration- and time-dependent inhibition of 500 microM domperidone was studied with 2.5-200 microM erythromycin over 10-40 min. Domperidone metabolite (5-hydroxy domperidone, M3) formation was inhibited by erythromycin in a concentration- and time-dependent manner. The K(I) estimate was 18.4 microM in human liver microsomes and 4.1 microM in CYP3A4. Using a model incorporating CYP3A4 hepatic and gut inhibition, in vitro estimates from human liver microsomes and CYP3A4 were used to predict in vivo AUCi/AUC ratios of 2.54 and 4.95, respectively. Significant inhibition of domperidone metabolism by erythromycin occurs. This predicts greater domperidone drug exposure when used with erythromycin. This important drug-drug interaction will be evaluated in future human studies.

A universal epitope-based influenza vaccine and its efficacy against H5N1.

Previous studies have shown that a recombinant vaccine expressing four highly conserved influenza virus epitopes has a potential for a broad spectrum, cross-reactive vaccine; it induced protection against H1, H2 and H3 influenza strains. Here, we report on the evaluation of an epitope-based vaccine in which six conserved epitopes, common to many influenza virus strains are expressed within a recombinant flagellin that serves as both a carrier and adjuvant. In an HLA-A2.1 transgenic mice model, this vaccine induced both humoral and cellular responses and conferred some protection against lethal challenge with the highly pathogenic H5N1 avian influenza strain. Hence, it is expected to protect against future strains as well. The data presented, demonstrate the feasibility of using an array of peptides for vaccination, which might pave the way to an advantageous universal influenza virus vaccine that does not require frequent updates and/or annual immunizations.

Early remodeling in an inducible animal model of retinal degeneration.

Photoreceptor degeneration is followed by significant morphological changes in the second-order retinal neurons in humans and in several genetic animal models. However, it is not clear whether similar changes occur when photoreceptor degeneration is induced nongenetically, raising the question whether these changes are a general effect of deafferentation independent of the cause of degeneration. We addressed this by inducing selective photoreceptor degeneration with N-methyl-N-nitrosourea (MNU) and studying its effects on inner retinal neurons in a mouse for up to 3 months, using immunocytochemistry and iontophoretic labeling. To develop objective measures of photoreceptor degeneration and of retinal remodeling, we measured several retinal proteins using immunoblot analysis, and quantified gross visual ability of the animal in a visual cliff test. The MNU-induced progressive degeneration of rods and cones was associated with declining levels of postsynaptic density 95 protein in the retina, and with deteriorating visual performance of the animal. Müller glial cells showed enhanced reactivity for glial fibrillary acidic protein as demonstrated by immunocytochemistry, which also reflected in increased levels of the protein as demonstrated by immunoblotting. Horizontal cells and rod bipolar cells progressively lost their dendritic processes, which correlated with a slight decline in the levels of calbindin and protein kinase C alpha respectively. Horizontal cell axons, immunoreactive for nonphosphorylated neurofilaments, showed sprouting into the inner nuclear layer. Ganglion cells and their synaptic inputs, probed by immunolocalizing beta-III-tubulin, neurofilaments, bassoon and synaptophysin, appeared to be unaffected. These results demonstrate that MNU-induced photoreceptor degeneration leads to retinal remodeling similar to that observed in genetic models, suggesting that the remodeling does not depend on the etiopathology that underlies photoreceptor degeneration.

The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies.

Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as 'transcriptase inhibitors', 'protease inhibitors', 'integrase inhibitors' and the more recent 'fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C-C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed.

Trans-resveratrol-mediated inhibition of beta-oestradiol conjugation in MCF-7 cells stably expressing human sulfotransferases SULT1A1 or SULT1E1, and human liver microsomes.

High concentrations of endogenous oestradiol (E2) correlate with the proliferation of cancer cells. Resveratrol (a dietary chemopreventive agent) at high concentrations has an anti-oestrogenic effect. E2 and resveratrol are conjugated via common uridine diphosphoglucuronosyltransferase (UGT) and sulfotransferases (SULT) enzymes. Experiments were conducted in MCF-7 mammalian cells stably expressing human SULT1A1 or SULT1E1 to observe the effect of resveratrol on E2-mediated cell proliferation. The combination of E2 and resveratrol did have a proliferative effect in cells expressing SULT1E1, but not in those expressing SULT1A1. The effect of resveratrol (1-500 microM) on the glucuronidation of E2 (0.25-2.25 microM) was characterized in human liver microsomes. The highest resveratrol concentration significantly decreased the intrinsic clearance of E2 glucuronidation. The results corroborate the reported significant inhibition of SULT1E1-mediated E2 sulfation in vitro by resveratrol. Thus, resveratrol may interact with E2 in vivo by inhibiting its conjugation.

Iron metabolism in the eye: a review.

This review article covers all aspects of iron metabolism, which include studies of iron levels within the eye and the processes used to maintain normal levels of iron in ocular tissues. In addition, the involvement of iron in ocular pathology is explored. In each section there is a short introduction to a specific metabolic process responsible for iron homeostasis, which for the most part has been studied in non-ocular tissues. This is followed by a summary of our current knowledge of the process in ocular tissues.

Lack of interaction between metoclopramide and morphine in vitro and in mice.

1. This study examined interactions via common metabolism or via common pharmacodynamic pathways between frequently co-prescribed metoclopramide (a prokinetic) and morphine (an opioid analgesic). 2. In human liver microsomes, morphine 3-glucuronide and morphine 6-glucuronide formation had V(max) estimates of 6.2 +/- 0.07 and 0.75 +/- 0.01 (nmole min(-1) mg(-1) protein) and K(m) estimates of 1080 +/- 37 and 665 +/- 55 (microM), respectively. The in vitro K(i) for morphine 3-glucuronide formation in the presence of metoclopramide in human liver microsomes or recombinant uridine diphosphoglucuronosyltransferase 2B7 predicted a lack of in vivo interaction. 3. Morphine (2 mg kg(-1) subcutaneously) delayed gastrointestinal meal transit in mice, metoclopramide (10 mg kg(-1) subcutaneously) had no effect on meal transit, and metoclopramide did not alter this effect of morphine. 4. Morphine (2 or 5 mg kg(-1) subcutaneously) was antinociceptive in mice (hot plate test) and metoclopramide (10 mg kg(-1) subcutaneously) did not alter the antinociceptive effects of morphine. 5. Together, the data suggest a lack of interaction between morphine and metoclopramide.

Epidemiology of animal bites and rabies cases in India. A multicentric study.

Rabies, a disease of antiquity continues to be a major public health problem in India. Multiple factors contribute to high mortality and morbidity due to animal bites. An effective strategy for control of rabies takes into account the epidemiology of animal bites, rabies and factors influencing post exposure treatment. The study was carried out as a part of Agreement for Performance of Work (APW) from World Health Organization (WHO) during the period April 2001 to September 2002. Two sets of proformae were developed and used after field testing to interview cases of animal bites and get retrospective information about rabies cases. The study was carried out at six selected centres across the country viz. Delhi, Hyderabad, Raipur, Jamnagar, Coonoor and Rajahmundry and was co-ordinated by National Institute of Communicable Diseases (NICD), Delhi. The officials engaged in the study work were thoroughly trained in the study methodology before the start of the study itself. To maintain quality and uniformity supervisory checks were done during the survey. A total of 1357 fresh animal bite victims were interviewed (exit interview) from the anti-rabies centres (ARCs). Dog bites caused maximum morbidity (92%). Second most common biting animal was monkey (3.2%), followed by cat (1.8%), fox (0.4%) etc. Most bites (64.3%) were unprovoked bites by stray (64.7%) animals. In this study 72.4% animal bite victims were males and 47.5% were children in age group of 2-18 years. 63% had Category III exposure as per the WHO classification. Before coming to ARCs 58.5% people had washed the wound with water/soap or water alone. Some of the bite victims (10.8%) had also applied chillies, salt, turmeric powder, lime, snuff powder, paste of leaves, acid, ash given by Peer Baba (magician) etc. These practices varied from one region to another. The practice of wound washing at the ARC which is an important component of animal bite management was being practiced at only one of the six centres. Of the six centres, Rabies Immunoglobulin (RIG) was available and was being used at only two centres. The study was conducted in public sector ARCs where Nervous Tissue Vaccine (NTV) was available free of cost. All the centres were using NTV except Coonoor, which is using indigenously produced Tissue Culture Vaccine along with NTV. Analysis of 192 case records of rabies cases, from two centres, revealed that dog bites caused maximum mortality (96.9%). Nearly 40% were children below 15 years of age and 78.6% were males indicating that it is an exposure related disease. In all cases, failure to seek timely and appropriate treatment led to development of disease. This paper provides an overview of epidemiology of animal bites and retrospective information about rabies patients. There is a need to strengthen Information, Education and Communication (IEC) programme regarding merits of local wound management including "do's and don'ts". ARCs should be strengthened in terms of facilities and availability of safe and effective anti rabies immunobiologicals. There is a need to create awareness regarding epidemiology and at-home and hospital management of animal bites among the service providers and general community.