Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

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CONTEXT: The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. AIM: This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. SETTINGS AND DESIGN: An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. MATERIALS AND METHODS: Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)_0–t, AUC_0–∞, C_max, and T_maxwere determined along with time above minimum inhibitory concentration (MIC). STATISTICAL ANALYSIS USED: The log-transformed PK parameters (C_max, AUC_0–t, AUC_0–∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. T_maxand MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. RESULTS: Geometric mean ratio of C_maxfell within bioequivalence criteria. The upper and lower confidence limits of both AUC_0–tand AUC_0–∞geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. CONCLUSIONS: The generic capsule was not bioequivalent to the branded amoxicillin capsule.

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OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA. RESULTS: There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.

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OBJECTIVES: Protease inhibitors are one of the most promising and investigated subjects for their role in pharmacognostical and pharmacological studies. This study aimed to investigate antineoplastic and antioxidant activity of trypsin inhibitors (TIs) isolated from three plant sources and their inhibitory role in the cell line. MATERIALS AND METHODOLOGY: TIs were obtained from different plant sources. Antineoplastic potential on adenocarcinoma human alveolar basal epithelial cell line (A549) and normal Human Embryonic Kidney (HEK) was determined using MTT assay. Activities of antioxidant enzyme, nitric oxide scavenger, superoxide dismutase, glutathione S-transferase, and glutathione peroxidase were assessed in cell lines incubated with and without TIs. The outcome was analyzed by spectrophotometer. RESULTS: TIs showed the higher cytotoxicity on A549 cells as compared to normal HEK cell line. TIs exhibited fair increase in antioxidant enzyme activity in A549 cells as compared to control. This might be one of the strategies of antineoplastic effect in cancer cells. CONCLUSIONS: This study has reported the antioxidant and antineoplastic properties of these TIs for the first time in A549 cells (to the best of our knowledge). The results show that TIs possess ability to prevent cancer and diseases caused due to oxidative stress. Therefore, we conclude that TIs can be used as supplements along with the conventional drugs for increased efficacy in the treatment of diseases such as cardiovascular disease, atherosclerosis, and cancer.

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OBJECTIVES: The objective of this study is to evaluate the impact of two educational interventions that are demonstration versus pictorial Leaflet in patients using metered-dose inhaler (MDI). MATERIALS AND METHODS: This interventional study was done in patients who were prescribed drugs through MDI at Tuberculosis and Chest Department. The patients were enrolled in Group A or Group B as per random number table method. The method of use of MDI was assessed using a checklist based on the technique described in the WHO Guide to good prescribing. Patients in Group A were taught the use of MDI by demonstration of the technique by the investigator. Patients in Group B were educated about the technique by a pictorial leaflet based on the technique. Patients were followed up after 15 days and assessed for correct technique for use of the MDI. RESULTS: A total 100 patients were included in the study and were allotted to Group A (47) and Group B (53). Ninety-five percent of the patients had been taught by the treating physician about the method of use of MDI. All the patients at the baseline placed the lips tightly around the mouthpiece and held the aerosol as indicated in the manufacturer's instructions while the step least followed was coughing up the sputum before inhalation. The average steps correctly followed by the patients in Group A and B at baseline were 5.17 ± 2.07 and 5.11 ± 2.04, respectively. These improved significantly to 9.19 ± 0.67 and 6.67 ± 0.63 in Group A and B, respectively, postintervention. The five essential steps of using MDI were followed by 25.53% and 26.41% patients preintervention. An improvement in the technique of use of MDI was observed in 85.11% and 49.06% patients (P = 0.003) postintervention. All the ten steps of the technique were followed by 34.04% patients from Group A and none from Group B at postintervention evaluation (P = 0.0001). CONCLUSION: The inhalation technique for the use of MDI used by the patients is inappropriate. Educational interventions such as demonstration or pictorial leaflet help ensure a better use of the MDI.

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OBJECTIVES: This study assessed statin use among diabetics and those with coronary heart disease (CHD) in Vellore, Tamil Nadu. METHODS: A cross-sectional survey was conducted in rural and urban Vellore, among 6196 participants (30–64 years), in 2010–2012. Statin use among those with known CHD and diabetes (on diabetic medication) was recorded. A randomly selected sample of rural diabetics was resurveyed in 2016 to reassess statin use. RESULTS: Among 61 with CHD, 23 (37.7%) were on statins. Statin use among 422 diabetics aged ≥40 years with low-density lipoprotein ≥70 mg/dl was 13.4% in urban and 7.6% among rural. Statin usage among rural diabetics aged ≥40 years increased from 7.7% in 2010–2012 to 16.6% in 2016. CONCLUSIONS: Statin use for CHD was below 50% although higher than the use among diabetics, indicating the need to address this low rate of usage among these high-risk groups.

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OBJECTIVES: The objective of this study is to evaluate the beneficial effect of karanjin for the treatment of experimental colitis. METHODS: Colitis was induced in the Balb/c mice by rectal administration of 2% solution of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 50% methanol. Karanjin (>98% pure) was administered in two different concentrations 100 and 200 mg/kg and sulfasalazine (100 mg/kg) as reference for 7 consecutive days to colitic mice. On the 8 day, mice were euthanized and degree of inflammation was assessed by macroscopic, microscopic, histology and biochemical estimation of myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) level were measured. RESULTS: Karanjin significantly and dose dependently ameliorate the macroscopic damage, histological changes such as cellular infiltration, tissue necrosis, mucosal and submucosal damage as compared to the TNBS control group. Karanjin reduces the activity of MPO, depressed MDA, and NO level and helps in restoring the level of CAT, SOD, and GSH to normal when compared to the TNBS colitis group. CONCLUSION: Result of the present study indicates that karanjin has the potential to cure colitis induced by intracolonic administration of TNBS.

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Chloroquine is the drug very frequently used for the treatment of malaria. It is also used in amebiasis, rheumatoid arthritis, and various dermatological conditions. Chloroquine can cause muscle problems, loss of appetite, and diarrhea as a side effect. Cutaneous toxicity includes pruritus, hair loss, photosensitivity, and color changes. Exfoliation of skin over palms and soles is caused by chemotherapeutic drugs such as axitinib, fluorouracil, idarubicin, doxorubicin, sunitinib, sorafenib, and paclitaxel. Here, a case of a 40-year-old female is presented who developed palmoplantar exfoliation with depigmentation after taking chloroquine. Although not life-threatening, this side effect of a commonly used drug may cause anxiety and functional impairment which in turn affects the quality of life of an individual.

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OBJECTIVE: Elsholtzia communis (Collett and Hemsl.) Diels has been widely distributed and is reported for many therapeutic effects. The present study aims to investigate the antistress activity of the leaf extract and its possible molecular mechanism. MATERIALS AND METHODS: Hydroethanolic extract of leaves of E. communis (100 and 200 mg/kg, p.o.) were administered for 7 days to stress-induced male Wistar rats. The experimental animals were divided into five groups (n = 6). The mRNA/protein profile of few stress responsive chaperones (hspa14), endoplasmic reticulum stress markers (C/EBP homologous protein [CHOP]), antioxidant regulating genes (nuclear factor (erythroid-derived 2)-like-2 factor [Nrf2]), apoptotic factors (Caspase-3) in rat hippocampus were studied by polymerase chain reaction and immunoblotting. RESULTS: The stress-related genes such as hspa14, CHOP, antioxidant gene Nrf2, apoptotic gene Caspase-3 which were overexpressed in the stress control group were significantly suppressed following administration of the extract at both the doses and the standard drug Ginseng. Likewise, brain-derived neurotrophic factor which is closely related with stress, was downregulated in the stress control group, was found to be upregulated following treatment with the extract and the standard drug Ginseng. CONCLUSION: Our findings clearly indicate that E. communis was able to counteract stress. Hence, it has the potential to develop as adaptogen and also as a replacement/substitute of the popularly used drug, Ginseng or Ashwagandha, which is on the verge of extinction or becoming endemic due to overuse.

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OBJECTIVES: The aim of this study is to analyze the availability and coverage by health insurance reimbursement of pediatric formulations labeled for children up to the age of 12 in Serbia. To provide good insight in general availability of pediatric medicines, results were compared with the World Health Organization's (WHO) “Model List of Essential Medicines for Children” and with published evidence. MATERIALS AND METHODS: Sources of information about medicines are the Summary of Product Characteristics, National Health Insurance Fund (NHIF) Drug Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official drug registry (2013). RESULTS: Out of total number of medicines in Serbia, only 49% (496) were available for children. Of all available drugs for children, 66% were with license and majority were parenteral formulation (57%), followed by drugs for local use (28%) and formulations for oral use (23%). The lowest availability of medicines was for children 0–27 days. From the total number of licensed medicines for children up to 12 years old, NHIF covers 64% of drugs. The availability of the WHO essential medicines for children in Serbia was 51%, from which 92% were licensed for pediatric use. CONCLUSIONS: Our results demonstrated the alarming lack of pediatric suitable formulations in Serbia. Significant differences in the availability of drugs suitable for children exist worldwide. From global health point of view, the differences in the access to children formulations should, therefore, be of the highest priority.

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