Phosphodiesterases (PDE) are exciting new targets in medical sciences. These enzymes are some of the key mediators of cellular functions in the body and hence are attractive sites for drug-induced modulations. With the finding that Tofisopam, a new anxiolytic, inhibits PDEs, the authors were inspired to look into the role of PDE and drugs acting on them in psychiatry. Hence, the review was undertaken. We found several research materials available highlighting the role of PDE in cellular functions and the possible newer etiological mechanisms of neuropsychiatric illnesses such as schizophrenia, depression/anxiety disorders, and cognitive dysfunction involving PDEs. We also found that there are many molecules acting on PDEs, which have the potential to alter the way we treat mental illnesses today. This article is intended to provide an in-depth look at these enzymes so that more cost-effective therapeutic molecules may be synthesized and marketed in India for managing mental illnesses.

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Introduction: Nonadherence to cardiovascular medicines is a major concern. It increases the morbidity and mortality of cardiovascular patients. The work was conducted to evaluate the adherence to cardiovascular medicines in patients of rural India. Methods: The study was conducted in the Department of Medicine involving rural patients with essential hypertension (HTN), congestive cardiac failure (CCF), and ischemic heart disease (IHD) over 12 months period. Patients were prescribed with cardiovascular medicines at the initial visit and adherence to medicines was assessed in the subsequent visit. Four items Morisky's Medication Adherence Scale (MMAS-4) was used for assessing medication adherence. Patients were considered adherent to medication if they answered negatively to all four questions. Results: Overall adherence to medication was 20.83%, 28.37% and 32% in HTN, CCF, and IHD patients, respectively. Nonadherence was highest in patients of HTN. Among the four reasons of nonadherence assessed by MMAS-4, carelessness was the most common and forgetfulness was the least common cause of nonadherence in all the three groups of patients. Conclusion: Patients of rural India adhere poorly to cardiovascular medicines. Nonadherence should be considered as a public health problem. Strategies for detecting the level of adherence of cardiovascular medicines, its barriers, and subsequent interventions should be developed by policy-makers to reduce morbidity and mortality due to cardiovascular disorders.

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Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity. Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically. Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA. Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.

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Objective: To evaluate adherence to medication and study factors associated with non-adherence in chronic kidney disease (CKD) patients. Methods: A prospective, cross-sectional, questionnaire based study was conducted in Nephrology department of a super specialty hospital. Patients above 18 years of age, suffering from CKD from six months or more were interviewed using self-designed, semi-structured questionnaire to get information about adherence to medication, diet restriction and lifestyle modification (n = 150). Morisky medication adherence questionnaire was used to calculate overall adherence. In this higher score indicates poor adherence. Main outcome measures included prevalence of non-adherence and factors associated with the same. Results: Average number of medicines taken by each patient was 8.0+1.612 (mean+SD) per day. Non-adherence to medication schedule was reported in 34% patients. Common causes of non-adherence were high cost (21.3%), complex dosing schedule (20%), fear of adverse effects (16%). Sixty-eight% patients were not aware about importance of taking each medicine. Sixteen% stopped taking medicines due to high cost. Forty-two% suggested that government should adopt measures to provide free medicines to poor patients. In Morisky medication adherence questionnaire high, medium and low adherence was reported in 7.3%, 55.3% and 37.3% of patients, respectively. Moderately positive correlation was observed between poor adherence and number of concurrent illnesses and number of medicines taken. Conclusion: Since majority of patients were not aware about importance of taking each medicine, creating awareness about the same is essential for improving adherence to therapy. Measures to provide free medicines to non-affording patients need to be implemented since high cost was other major cause of non-adherence.

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Objective: Rheumatoid arthritis (RA) is characterized by symmetric peripheral polyarthritis, inflammatory synovitis, and articular destruction. Statins, 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, mediate significant vascular risk reduction in patients with coronary artery disease by promoting reduction in plasma levels of low-density-lipoprotein cholesterol. Extensive in vitro data, experimental studies and more recently few clinical trials have strongly suggested statins to possess an important role in RA mainly mediated by their anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the effect of adjunct statin therapy in comparison to standard disease modifying antirheumatic drugs (DMARD) therapy in patients with RA. Materials and Methods: In this observational study, diagnosed RA patients of age group between 40 and 60 years were selected as per the inclusion criteria from the rheumatology outdoor. From the selected patients, we identified two separate groups of patients. Group 1 included 30 patients of RA currently under DMARD therapy with adjunct statin medication. Group 2 included 30 patients of RA currently under DMARD therapy. Patients were followed up over 6 months. Standard parameters such as disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded for comparing the outcome of RA in both groups. Results: Out of a total of 60 patients who took part in the study, significant beneficial role of adjunct statin medication was found in this study when prescribed along with conventional DMARDs in active RA patients. The mean DAS28, considered by far as the most important index of clinical disease activity in RA, was found to be significantly lower (P < 0.05) in the adjunct statin-treated group (group 1) than that of the conventional DMARD treated group (group 2) after 6 months of continuous therapy. Other two important biochemical markers of RA disease activity, that is, ESR and CRP were also found to be significantly lower (P < 0.05) in RA patients who were on adjunct statin medication (group 1) than in group 2 comprising RA patients only under conventional DMARDs therapy without statin medication. Conclusion: The results suggest an adjunct and potentially beneficial role of statin therapy in active cases of RA, producing significant clinical and biochemical improvement.

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Aim: Black grape peel possesses a substantial amount of polyphenolic antimicrobial compounds that can be used for controlling the growth of pathogenic microorganisms. The purpose of this study was to assess antibacterial and antifungal activity of black grape peel extracts against antibiotic-resistant pathogenic bacteria and toxin producing molds, respectively. Materials and Methods: Peel of grape was subjected to polyphenolic extraction using different solvents viz., water, ethanol, acetone, and methanol. Antibiotic-resistant strains of Staphylococcusaureus,Enterococcusfaecalis, Enterobacteraerogenes,Salmonella typhimurium, and Escherichiacoli were screened for the antibacterial activity of different grape extracts. Antibacterial activity was analyzed using agar well diffusion method. Penicilliumchrysogenum, Penicilliumexpansum, Aspergillusniger and Aspergillusversicolor were screened for the antifungal activity. Antifungal activity was determined by counting nongerminated spores in the presence of peel extracts. Results: As compared to other solvent extracts, methanol extracts possessed high antibacterial and antifungal activity. S.typhimurium and E. coli showed complete resistance against antibacterial action at screened concentrations of grape peel extracts. Maximum zone of inhibition was found in case of S.aureus, i.e., 22 mm followed by E.faecalis and E.aerogenes, i.e., 18 and 21 mm, respectively, at 1080 mg tannic acid equivalent (TAE)/ml. The maximum and minimum percent of growth inhibition was shown by P.expansum and A.niger as 73% and 15% at 1080 TAE/ml concentration of grape peel extract, respectively. Conclusions: Except S.typhimurium and E.coli, growth of all bacterial and mold species were found to be significantly (P < 0.05) inhibited by all the solvent extracts.

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Comparative effectiveness research (CER) is an important branch of pharmacoeconomics that systematically studies and evaluates the cost-effectiveness of medical interventions. CER plays instrumental roles in guiding government public health policy programs and insurance. Countries throughout the world use different methods of CER to help make medical decisions based on providing optimal therapy at a reduced cost. Expenses to the healthcare system continue to rise, and CER is one-way in which expenses could be curbed in the future by applying cost-effectiveness evidence to clinical decisions. China, India, South Korea, and the United Kingdom are of essential focus because these country's economies and health care expenses continue to expand. The structures and use of CER are diverse throughout these countries, and each is of prime importance. By conducting this thorough comparison of CER in different nations, strategies and organizational setups from different countries can be applied to help guide public health and medical decision-making in order to continue to expand the establishment and role of CER programs. The patient-centered medical home has been created to help reduce costs in the primary care sector and to help improve the effectiveness of therapy. Barriers to CER are also important as many stakeholders need to be able to work together to provide the best CER evidence. The advancement of CER in multiple countries throughout the world provides a possible way of reducing costs to the healthcare system in an age of expanding expenses.

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Objectives: This study aimed to identify the current knowledge, attitude, and perception (KAP) of the future prescribers about antimicrobial (AM) education so that the identified lacunae in the training curriculum can be effectively addressed. Materials and Methods: A questionnaire-based survey was carried out in the 2^nd year students of medical and the dental undergraduate (UG) courses at a tertiary care teaching center in Jaipur. Each respondent completed the given questionnaire independently in the allocated time. A scoring system was used to rate the KAP of the respondents as poor, average, or good. Results: Statistically significant differences were found in the KAP of the medical and dental future prescribers (P = 0.0086, 0.0002, and <0.0001 for the KAP, respectively). Conclusion: The attitude of the UG students towards AM education is good, but the deficiencies in the knowledge and perception need to be improved further. Suitable interventions to address these lacunae must be planned.

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Objective: Ficus racemosa (FR) is one of the herbs mentioned in the scriptures of the Ayurveda as Udumbara with high medicinal value. The objective of this study was to estimate the protective effect of FR against streptozotocin (STZ) induced diabetic neuropathy with neurodegeneration (DNN). Materials and Methods: Diabetes was induced in Wistar rats with STZ and were divided into six groups namely diabetic vehicle control, FR (four) and glibenclamide (one) treated rats; while one group was of normal control rats. After the 4^th week of diabetes, induction treatment was started for further 28 days (5^th to 8^th week) with FR aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Investigation of DNN was carried out through biochemical and behavioral parameter assessment in rats. Results: Study showed a significant fall in glycosylated hemoglobin (HbA1c) and blood glucose level by the treatment of FR in diabetic rats. Antioxidant potential of FR showed a great rise in superoxide dismutase, catalase content and reduction observed in serum nitrite level; while significant fall in lipid peroxidation level and of C-reactive protein was observed in FR treated diabetic rats. Further FR treated diabetic rats also showed marked improvement in tail flick latency, pain threshold, the rise in locomotion and fall latency period. Conclusion: Treatment with FR shows protection in the multiple pathways of DNN by improving blood glucose, HbA1c, biochemical, and behavioral parameters, which suggest the protective role of FR in the reversal of DNN.

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Drug-induced hair loss may occur as a side effect in patients treated with valproate. However, few studies have reported a relationship between the blood levels of valproate and the occurrence of hair loss. We report three cases of alopecia that occurred in patients who received sodium valproate for mental disorders. In all three cases, alopecia appeared after long-term valproate exposure with a plasma concentration of 100 µg/ml approximately. However, the alopecia resolved in all cases after dose reduction or treatment discontinuation. Therefore, alopecia may develop in patients with chronic exposure to high plasma concentrations of valproate. Based on these findings, we believe that patients with high plasma concentrations of valproate should be closely monitored for the occurrence of side effects, particularly alopecia.

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Terbinafine is an allylamine antifungal agent which is widely used for the treatment of fungal infections. Cutaneous side effects have been reported in 2% of the patients on terbinafine therapy with many morphological patterns. We report a case of terbinafine induced pityriasis rosea, a very rare side effect of terbinafine. This report emphasizes the importance of counseling the patient to report immediately in the event of a cutaneous eruption.

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Objectives: To investigate if fluoroquinolones (FQs) influence skeletal muscle metabolism of healthy and malignant hyperthermia susceptible (MHS) pigs. Materials and Methods: After approval from of the Animal Care Committee, 10 MHS pigs, and 6 MHS pigs were anesthetized with hemodynamic and systemic metabolic monitoring. Microdialysis catheters were placed intramuscularly. After equilibration, levofloxacin and ciprofloxacin were injected as a rapid bolus and continuous infusions. Lactate was measured in the dialysate and statistically analyzed was done (Wilcoxon-test; U-test;P < 0.05). Results: There were no differences in age, weight, and baseline lactate levels between the groups. Both applications of levofloxacin- and ciprofloxacin-induced an increase of local lactate levels in healthy and MHS pigs. No difference between the two groups was observed. Conclusion: FQs influence skeletal muscle metabolism. Myotoxic effects of FQs can, therefore, be explained by an influence on the cellular energy balance.

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Objective: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. Materials and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. Statistical Analysis: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. Results: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. Conclusion: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy.

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Objective: The study is aimed to evaluate anti-inflammatory activity of Caesalpinia bonducella Fleming (Caesalpiniaceae) flower extract (CBFE) and to study its effect on radiographic outcome in adjuvant induced arthritis and authentication by high performance thin layer chromatography (HPTLC) chemical fingerprinting. Materials and Methods: CBFE was administered orally (30, 100, and 300 mg/kg b.wt.) and tested for its anti-inflammatory activity in carrageenan-induced inflammation, cotton pellet induced chronic granulomatous inflammation and autacoids-induced inflammation. Effect on radiographic outcome was tested in adjuvant-induced arthritis. CBFE was HPTLC fingerprinted in suitable solvent system. Result: In carrageenan-induced inflammation, CBFE produced significant inhibition in edema volume at all the doses (30, 100 and 300 mg/kg b.wt.) and percentage of inhibition was 28.68, 31.00, and 22.48, respectively as compared to control at 5 h of its administration. In cotton pellet granuloma assay, CBFE significantly decreased the granuloma weight at 300 mg/kg dose level by 22.53%. CBFE (300 mg/kg) caused significant inhibition by 37.5, 44.44, and 35.29% edema volume, at ½, 1 and 3 h after 5-hydroxytryptamine injection, respectively. Radiographic score of animals treated with 300 mg/kg CBFE was significantly decreased when compared to arthritic control animals. Conclusion: The extract was found to possess significant anti-inflammatory activity. CBFE treatment improved the bony architecture in adjuvant-induced arthritis in rats. The developed HPTLC fingerprint would be helpful in the authentication of C. bonducella flower extract.

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Objective: The ability of Luffa cylindrica Roem fruit extract (LCE) to modulate biochemical parameters was investigated by in vitro studies for its role in hydrogen peroxide induced cataract on isolated goat lenses which were incubated for 72 h at 37°C. Materials and Methods: Test groups contained 5, 10, 15, 20, 25, and 30 µg/ml of LCE along with 1 ml of H₂O₂ (0.5 mM) as cataract inducer. Lenses were examined for morphological variation and transparency periodically during the incubation. Biochemical parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), total protein content (TPC), and malondialdehyde (MDA) were estimated. Results: SOD, GSH, and TPC levels were found to increase proportionally with the concentration of LCE. However, MDA levels were found to be inversely proportional to the concentration of LCE. Opacity was graded as per “lens opacities classification system III.” Morphological examination suggested that LCE (25 µg/ml) maintained a vision for 44 h. No lens in LCE dose groups developed dense nuclear opacity after 24 h as opposed to 80% in negative control. Conclusion: The results suggest that LCE can delay the onset and/or prevent the progression of cataract which can be attributed to the presence of adequate phenolics, flavonoids, and Vitamin A and its high nutritional value. This preliminary study can be further synergized by testing LCE against other in vivo and in vitro models of cataract.

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Aim: Despite having better tolerability and a wide range of clinical applications over other antidepressants, selective serotonin reuptake inhibitors (SSRIs) are also known to be associated with serious adverse effects like suicidal ideation on chronic use. The present study had explored the impact of the chronic use of sertraline, an SSRI, on the behavioral changes in Wistar albino rats. Materials and Methods: The study was conducted on 30 Wistar albino rats of either sex; divided into five groups. Four groups were subjected to chronic mild stress induced by using various stressors randomly scheduled in a week and continued for a period of 3 weeks. The stressed rodents were subjected to sertraline treatment for 9 weeks in different human therapeutic doses extrapolated to animal doses. Behavioral changes were monitored, assessed, and evaluated throughout the treatment phase with the help of tests such as locomotor activity test, forced swim test, tail suspension test, antianxiety test, and sucrose preference test (SPT). Results: All tests except SPT, demonstrated significant (P < 0.05) reduction in depressive-like activity in the stressed rodents by the mid-treatment phase, followed by an abrupt onset of the depressive state by the end of the treatment phase. SPT showed a significant (P < 0.05) increase in sucrose consumption throughout the treatment phase. Conclusion: Behavioral changes following chronic sertraline administration conferred gradual remission of depression state on initial treatment phase, followed by a reversal of effect on chronic use.

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Tuberculosis is a common infectious disease in developing countries. Isoniazid is established the first-line antitubercular drug and an essential component of all antitubercular regimens. Erythroderma caused by isoniazid is an uncommon but serious adverse drug reaction. We report here a case of a 63-year-old female patient who presented with generalized redness and scaling with itching after 8 weeks of antitubercular treatment (ATT). ATT was stopped immediately, and antihistaminics were started. The patient improved over a period of 2 weeks. On sequential rechallenge, she developed similar lesions all over the body with isoniazid, hence confirming the diagnosis of isoniazid-induced erythroderma.

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Objectives: Quercetin exhibits a wide range of biological functions. The present study aimed to investigate the possible beneficial effects of rosiglitazone, quercetin as well as their combination on metabolic and biochemical changes associated with the fructose-induced metabolic syndrome (MS). Materials and Methods: Four groups of rats were fed on fructose-enriched diet for 14 weeks. One group served as fructose-enriched diet control, while the remaining groups were treated with rosiglitazone (4 mg/kg/day), quercetin (50 mg/kg/day), and their combination during the last 4 weeks. A fifth group was fed on normal laboratory diet. At the end of the experiment, blood samples were withdrawn for the estimation of markers of MS. Results: Rosiglitazone or quercetin attenuated the biochemical and metabolic changes associated with MS. The combination of rosiglitazone and quercetin nearly normalized these changes. Conclusion: Quercetin, as well as its combination with rosiglitazone, showed beneficial protective effects against metabolic and biochemical changes associated with MS.

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Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, mostly induced by drugs. Hydroxychloroquine have been rarely reported in literature as a causative drug of this reaction. We report a case of AGEP induced by hydroxychloroquine with systemic involvement and confirmed by positive patch testing.

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Objective: To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved. Materials and Methods: YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability. Results: The results showed that the body weight of colitis mice was markedly decreased by 10, 12, 14, and 17% at 1, 3, 5, and 7 days (P < 0.05), whereas stool consistency score (3.6 vs. 0.4, P < 0.05), histopathological score (3.6 vs. 0.3, P < 0.05), and MPO activity (2.7 vs. 0.1,P < 0.05) in colitis mice were significantly increased compared to that of the normal mice; YPF powder treatment dose-dependently increased the body weight (7–13% increase) and decreased the stool consistency score (0.4–1.4 decrease), histopathological score (0.2–0.7 decrease), and MPO activity (0.1–0.9 decrease) in colitis mice. Colonic EC cell density (70% increase) and 5-HT content (40% increase) were markedly increased in colitis mice (P < 0.05), YPF powder treatment dose-dependently reduced EC cell density (20–50% decrease), and 5-HT content (5–27% decrease) in colitis mice. Conclusion: The findings demonstrate that the anti-inflammatory effect of YPF powder on TNBS - induced colitis may be mediated via reducing EC cell hyperplasia and 5-HT content. The important role of YPF powder in regulating colonic EC cell number and 5-HT content may provide an alternative therapy for colonic inflammation.

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Aim: To correlate the level of anxiety with nonadherence to antiretroviral medication. Materials and Methods: This observational, cross-sectional, hospital-based study was conducted in 78 patients attending antiretroviral therapy (ART) center of a tertiary care hospital of Odisha. The study duration was 6 months. Patients were designated as nonadherent by referring to the white card. Utilization of ART drugs and adverse drug reactions were included in a predesigned format. The anxiety level of all included patients was scored as per Hamilton Anxiety Rating Scale. Mean anxiety score of the adherent group was compared with that of the nonadherent group. Possible causes of nonadherence leading to high anxiety level were evaluated. Results: 46% of patients in the nonadherent group had very severe, 17% had moderate to severe, 28% had mild to moderate and 9% had a mild level of anxiety. In the adherent group, however, mild to moderate level of anxiety was observed only in 10% patients. Conclusions: Anxiety is associated with sub-optimal medication adherence in HIV infected patients.

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The course of chronic myeloid leukemia (CML) has changed since the introduction of imatinb, and its side-effects are still being reported. We are reporting a case of a CML patient who presented to us with discoloration of the upper front teeth following 6 months of therapy with imatinib. On detailed evaluation, the patient was found to have imatinib-induced dental hyperpigmentation.

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Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal.

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