Human Monkeypox Virus and Host Immunity: New Challenges in Diagnostics and Treatment Strategies.

The monkeypox virus (MPXV), responsible for human disease, has historically been limited to the African countries, with only a few isolated instances reported elsewhere in the world. Nevertheless, in recent years, there have been occurrences of monkeypox in regions where the disease is typically absent, which has garnered global interest. Within a period of less than four months, the incidence of MPXV infections has surged to over 48,000 cases, resulting in a total of 13 deaths. This chapter has addressed the genetics of the pox virus, specifically the human monkeypox virus, and its interaction with the immune systems of host organisms. The present chapter is skillfully constructed, encompassing diagnostic methodologies that span from traditional to developing molecular techniques. Furthermore, the chapter provides a succinct analysis of the therapeutic methods employed, potential future developments, and the various emerging difficulties encountered in illness management.

The evaluation of efficacy and safety of methotrexate and pioglitazone in psoriasis patients: A randomized, open-labeled, active-controlled clinical trial.

OBJECTIVES: Psoriasis is a chronic inflammatory disease showing co-existence with metabolic syndrome (MS), as has been confirmed by numerous epidemiologic studies in recent times. In this study, the aim was to ascertain the beneficial effects of pioglitazone in psoriasis, simultaneously targeting the improvement of MS parameters. MATERIALS AND METHODS: We conducted a prospective randomized open-labeled parallel-group interventional study in patients of moderate-to-severe chronic plaque psoriasis. A total of 90 patients were inducted in study and divided into three groups of standard treatment (methotrexate 7.5 mg/week for 12 weeks), active treatment (pioglitazone 15 mg tablets once daily for 12 weeks), and their combination. Primary outcome was taken as percentage Psoriasis Area and Severity Index (PASI) improvement from baseline; secondary outcomes were PASI-75, safety profile, and MS parameters. RESULTS: Intergroup evaluation of PASI score showed that standard treatment methotrexate and active treatment pioglitazone were comparable. Combination of methotrexate and pioglitazone proved superior in efficacy from both standard and active treatment in 8 and 12 weeks. Adverse drug reactions were mild and treated symptomatically. Pioglitazone and combination group also demonstrated beneficial efficacy in parameter of MS hence establishing it as a potential therapy in psoriasis with MS. CONCLUSIONS: Pioglitazone alone or in combination with standard treatment may be a safe alternative drug for psoriasis coexisting with MS proving beneficial for both.

Workshop on Adverse Drug Reaction Reporting, Pharmacovigilance and Its Implementation in Cancer Hospital in Nepal: An Event Report.

Adverse drug reactions are crucial events related to drug usage that ought to be reported and the effects of which can be minimized by careful and vigilant use of drugs. Pharmacovigilance refers to the systematic practice of reporting, assessing and preventing such events. Although such practice is vital in any healthcare system, its actual implementation has been found to be very limited in a country like Nepal. With the aim of disseminating information about such events and the role of healthcare professionals in pharmacovigilance, a one-day workshop was organized with international and national speakers on this subject at Nepal Cancer Hospital and Research Center, Lalitpur, Nepal, which also has a regional pharmacovigilance center . The workshop included lectures and hands-on training and had an audience from diverse fields of healthcare such as pharmacy, medical, surgical and radiation oncology, pathology and nursing staff. The feedback from the participants revealed that practical demonstration and hands-on training with extensive topic coverage were the best feature of the workshop, while less interaction during the lectures was a source of dissatisfaction with a recommendation to conduct more events focused on similar topics in the future.

Lifitegrast: A novel drug for treatment of dry eye disease.

Dry eye disease (DED) is an inflammatory disorder of ocular surfaces leading to severe disability, especially in the elderly age group. The mainstay of therapy includes artificial tears, punctual plugs, topical anti-inflammatory agents, and corticosteroids. In the past few years, only cyclosporine-A emulsions have been added to the existing therapy, but it is discontinued by most patients as it causes burning sensation in the eye. Hence, progress in new research for a better therapeutic option led to the discovery of lymphocyte function-associated antigen intercellular adhesion molecule 1 antagonist, lifitegrast. It hinders the T-cell activation, release of inflammatory mediators, and consequently inhibits the inflammatory pathways in DED. It was approved by the US Food and Drug Administration in July 2016 for the treatment of DED. This review highlights the development process and approval of lifitegrast.

Evaluation of Efficacy of Curcumin as an Add-on therapy in Patients of Bronchial Asthma.

BACKGROUND: Bronchial asthma being a chronic inflammatory disease of airways has numerous treatment options none of which have disease modifying properties. Curcumin, a yellow dietary pigment has varied pharmacological activities, prominent among which is an anti-inflammatory activity which may be crucial in bronchial asthma as has been proved by various in vitro and in vivo animal studies. AIMS: To determine the efficacy and safety of curcumin as an 'add-on' therapy in patients of bronchial asthma. SETTINGS AND DESIGN: This study was conducted on 77 patients of mild to moderate Bronchial asthma who had a documented positive bronchodilator reversibility test with ≥15% improvement in forced expiratory volume one second (FEV1). MATERIALS AND METHODS: Seventy seven patients were recruited for the study and randomized into either of the two groups, but 17 patients were lost to follow up. Thus Group A - Receiving standard therapy for bronchial asthma for 30d (n=30) and Group B - Receiving standard therapy for bronchial asthma + Cap Curcumin 500mg BD daily for 30d (n=30). The predefined primary endpoints were clinical assessments of dyspnoea, wheezing, cough, chest tightness and nocturnal symptoms, change in the pre-bronchodilator FEV1 during the treatment and hematological improvement. The secondary end points were assessed by the change in the post-bronchodilator FEV1, C-reactive protein (CRP) concentration and incidence of adverse events. STATISTICAL ANALYSIS USED: The data was analysed by SPSS 17.0 software using one-way ANOVA or Paired t-test. RESULTS AND CONCLUSION: The results showed that curcumin capsules help in improving the airway obstruction which was evident by significant improvement in the mean FEV1 values. There was also significant improvement in the hematological parameters and absence of any clinically significant adverse events indicates dependable safety profile of curcumin capsules, though there was no apparent clinical efficacy. Therefore, it is concluded that curcumin is effective and safe as an add-on therapy for the treatment of bronchial asthma.

Hedgehog signaling pathway: a novel target for cancer therapy: vismodegib, a promising therapeutic option in treatment of basal cell carcinomas.

The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC) and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449), an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib.

Cabazitaxel: A novel taxane for metastatic castration-resistant prostate cancer-current implications and future prospects.

Recent advances in the management of prostate cancer have shown considerable development with time and many novel therapeutic agents have been approved over the past years. For patients with metastatic castration-resistant prostate cancer (mCRPC), initially docetaxel was the standard chemotherapy but once they became refractory to docetaxel, no treatment improved survival. This scenario changed in June 2010 when the US Food and Drug Administration (FDA) approved Cabazitaxel as a new therapeutic option for patients with mCRPC resistant to docetaxel. Cabazitaxel, being a novel tubulin-binding taxane with poor affinity for P-glycoprotein, decreases the chances of resistance. It has shown antitumor activity in preclinical, phase I, II and III clinical studies in docetaxel-resistant tumors. This article summarises the background, pharmacodynamic, kinetics and clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer. Future development and rational use of this drug in other tumors is under therapeutic investigation.

Comparative evaluation of topical calcipotriol versus coal tar and salicylic acid ointment in chronic plaque psoriasis.

BACKGROUND: Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use. AIMS: To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis. SETTING and DESIGNS: Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital. METHODS: The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse. STATISTICAL ANALYSIS: It was done by paired t-test and independent sample t-test. CONCLUSIONS: The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

A comparative clinical evaluation of once daily versus alternate day application of topical clobetasol propionate cream in psoriasis.

BACKGROUND: Corticosteroids are extremely useful in the treatment of inflammatory skin disorders. Topical steroid applications are the most effective treatment for all types of psoriasis. AIMS: To compare the efficacy of once daily versus alternate day application of topical steroid clobetasol propionate 0.05% (Tenovate cream®) in patients who have mild to moderate plaque psoriasis. SETTINGS AND DESIGN: This study was conducted on 89 patients of plaque psoriasis, who attended the skin OPD in our hospital. METHODS AND MATERIAL: The patients who had a mild to moderate severity of plaque psoriasis were selected. Those patients who required systemic corticosteroids, those who were already undergoing any psoriasis treatment, those who had any other debilitating illness and pregnant and lactating women were excluded from the study. Eighty nine patients were enrolled for the study after taking written informed consent from them and they were randomly allocated into two groups. Two patients dropped out, one in each group and 1 of group 2 was prescribed systemic corticosteroids.Group 1- once daily application (n= 44)Group 2- alternate day application (n= 42)An objective scoring was done on the basis of the PSI (Psoriasis Severity Index) score, which was graded from 0-4. Follow ups were done in the 2nd, 4th and 6th weeks. STATISTICAL ANALYSIS: It was done by the Student's 't' test and ANOVA. RESULTS AND CONCLUSIONS: The results showed that there was equal improvement in both the groups in the 2nd week, since the p-value was not significant (P> 0.05), but in the 4th and 6th weeks, there was less improvement in the alternate day group (P< 0.05). An intra group comparison indicated that clobetasol was effective both in the once daily and the alternate day groups, but clinical and symptomatic improvement occurred more quickly in the once daily group after 6 weeks of assessment. Thus, it can be concluded that the alternate day application of the topical steroid clobetasol propionate cream is as effective as the once daily application in the initial 2 weeks, but by 6 weeks, its efficacy decreases. Therefore, initially, we can advocate a less frequent application of potent topical steroids but for the complete remission of the disease, the application frequency should be once daily.

Comparison of reservoir effect of topical corticosteroids in an experimental animal model by histamine-induced wheal suppression test.

INTRODUCTION: Topical corticosteroids used in various dermatological diseases are available in different potencies and different formulations. The reservoir effect of different potency corticosteroids in the stratum corneum will help the clinicians to choose an appropriate topical steroid to maximize their efficacy and safety as therapeutic agents. AIMS: This study was designed to compare the duration of reservoir of different potency topical corticosteroids experimentally in rabbits using histamine-induced wheal suppression test. MATERIALS AND METHODS: The study was carried out in albino rabbits (as their skin is similar to humans) using four different concentrations of topical steroids, namely mometasone furoate ointment (0.1%), fluticasone propionate ointment (0.005%), betamethasone valerate cream (0.1%), and hydrocortisone butyrate cream (0.1%). These were applied on the back of rabbit on one side and the vehicle was applied on the other. One hour later, histamine-induced wheal suppression test was performed on both sides and wheal area was measured at 10 min for 7 days. Statistical analysis was done by ANOVA followed by post hoc test. RESULTS: Maximum wheal suppression was seen on day 1 (P<0.001) in all four groups, both at test and at control sites. Interday comparison of mean wheal size by topical steroids showed that the reservoir of mometasone furoate ointment (0.1%) persisted till day 4 in the stratum corneum of the skin. In case of fluticasone propionate ointment (0.005%) and betamethasone valerate cream (0.1%), the reservoir persisted till day 2 and for hydrocortisone butyrate cream (0.1%), the reservoir was present only on day 1. CONCLUSIONS: It is concluded that the duration of reservoir depends on the potency of topical steroids. Higher the potency more is the duration of reservoir in stratum corneum and vice versa.

Study of reservoir effect of clobetasol propionate cream in an experimental animal model using histamine-induced wheal suppression test.

BACKGROUND: Topical corticosteroids used in various dermatological diseases several times a day led to an increase risk of side effects. By demonstrating a significant reservoir of corticosteroids in the stratum corneum, one can maximize their efficacy and safety as therapeutic agents. AIM: The study was designed to demonstrate a reservoir of topically applied corticosteroid clobetasol propionate cream experimentally in rabbits using histamine-induced wheal suppression test. MATERIALS AND METHODS: The work was carried out on albino rabbits, as rabbit skin is akin to human skin, using a topical steroid. The topical steroid clobetasol propionate 0.05% cream was applied on the back of rabbit, and after 1-h occlusion histamine-induced wheal suppression test was performed and wheal area measured at 10 min till day 7. Statistical analysis was done by ANOVA followed by "Post Hoc" test. RESULTS: Maximum wheal suppression was seen on day 1 (P < 0.001). Interday comparison of mean wheal size showed no significant difference (P > 0.05) on day 2, 3, and 4 as compared to day 1. Day 5-7 show highly significant difference (P < 0.001) as compared to day 1, thereby suggesting that the reservoir effect of topical clobetasol propionate 0.05% cream persisted till day 4. CONCLUSIONS: This work demonstrated that histamine-induced wheal by the topical steroid clobetasol propionate 0.05% cream was suppressed till day 4, indicating that the reservoir of topical corticosteroid persisted till day 4.