Amplification of Cardioprotective Response of Remote Ischemic Preconditioning in Rats by Quercetin: Potential Role of Activation of mTOR-dependent Autophagy and Nrf2.

OBJECTIVES: Noninvasive remote ischemic preconditioning (RIPC) is a practical, acceptable, and feasible conditioning technique reported to provide cardioprotection in myocardial ischemia-reperfusion injury (MIRI). It has been well-reported that quercetin possesses antioxidant and anti-inflammatory properties. This study investigates the modification of the cardioprotective response of RIPC by quercetin. METHODS: Adult Wistar rats were randomized into 12 groups of six animals each. MIRI was induced by subjecting the isolated hearts of Wistar rats to global ischemia for 30 min, succeeded by reperfusion of 120 min after mounting on the Langendorff PowerLab apparatus. Hind limb RIPC was applied in four alternate cycles of ischemia and reperfusion of 5 min each by tying the pressure cuff before isolation of hearts. RESULTS: MIRI was reflected by significantly increased infarct size, LDH-1, and CK-MB, TNF-α, TBARS, and decreased GSH, catalase, and hemodynamic index, and modulated Nrf2. Pretreatment of quercetin (25 and 50 mg/kg; i.p.) significantly attenuated the MIRI-induced cardiac damage and potentiated the cardioprotective response of RIPC at the low dose. Pretreatment of ketamine (10 mg/kg; i.p.), an mTOR-dependent autophagy inhibitor, significantly abolished the cardioprotective effects of quercetin and RIPC. CONCLUSIONS: The findings highlight the modification of the cardioprotective effect of RIPC by quercetin and that quercetin protects the heart against MIRI through multiple mechanisms, including mTOR-dependent activation of autophagy and Nrf-2 activation.

Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia.

This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.

Utility of Dermoscopy in the Diagnosis of Erythroderma: A Cross-Sectional Study.

Background: It is difficult to diagnose the underlying cause of erythroderma on mere clinical presentation. The role of dermoscopy in diagnosing erythroderma secondary to various etiologies is evolving. Aim and Objectives: This study aimed to observe the dermoscopic features of erythroderma secondary to different cutaneous disorders and compare them with clinical features and histopathology. Materials and Methods: Twenty-nine consecutive patients of erythroderma were enrolled in the study. Dermoscopy was performed on every case using a Heine Delta II Dermatoscope with 10x magnification in polarized mode. A histopathological examination was conducted to confirm the diagnosis. Results: Eight patients were diagnosed with psoriasis, five with endogenous eczema, four with pityriasis rubra pilaris (PRP), three with pustular psoriasis, two with drug rash secondary to antitubercular therapy, two with dermatophytic infection, one patient each of atopic dermatitis, crusted scabies, pemphigus foliaceous, drug reaction with eosinophilia and systemic symptoms, and mycosis fungoides. Characteristic dermoscopic features were observed in erythroderma due to psoriasis, PRP, pustular psoriasis, endogenous eczema, scabies, and dermatophytosis. Differentiation of other disorders based on dermoscopy alone was difficult, and clinico-histopathological correlation was crucial to reach a diagnosis. Conclusion: Dermoscopic features of classical patterns of skin disorders are preserved even in the corresponding erythrodermic or unstable stage. Dermoscopic features of erythroderma secondary to psoriasis, pustular psoriasis, PRP, endogenous eczema, scabies, and dermatophytosis are clearly differentiating, whereas the dermoscopic features in other causes of erythroderma are overlapping. Thus, dermoscopy can be a good screening tool in the clinical assessment of erythroderma.

Erosive pustular dermatosis of the scalp secondary to Erlotinib: A rare occurrence with trichoscopic perspective.

Epidermal growth factor receptor inhibitors are anti-tumour agents that are frequently used for the treatment of neoplastic disorders. In addition to their cutaneous adverse effects, these drugs can rarely lead to erosive pustular dermatosis of the scalp. We report a case of a 67-year-old female who developed erosive pustular dermatosis of the scalp after being started on erlotinib from a trichoscopic perspective, which has been described in literature only once till now.

Are we moving from symptomatic to asymptomatic syphilis: A retrospective analysis.

Background: Syphilis remains a global health problem with recent reports of resurgence from various parts of the world. We undertook this study to analyze the current epidemiological and clinical trends of syphilis in our part of the country. Aim and Objectives: To analyze the changing trends in clinical presentation of syphilis and the current status of HIV/AIDS-syphilis co-infection in our area. Materials and Methods: This is a hospital-based retrospective analysis of records of sexually transmitted disease (STD) patients enrolled in "Suraksha clinic" in the department of Skin and VD at a Tertiary Care Hospital in North India. Patient records were analyzed from January 2018 to December 2021. The demographic, clinical, and serological profiles of patients were assessed to study the percentage of syphilis patients attending the STD clinic and their clinical presentations. Results: A total of 7153 patients were enrolled in the"Suraksha clinic" from January 2018 to December 2021, these included the venereal disease patients (3137) and nonvenereal disease patients (4016) who were registered for HIV and venereal disease research laboratory (VDRL) screening from the dermatology outpatient department. Out of 3137 sexually transmitted infection (STI) patients, 139 patients tested positive for VDRL. Treponema pallidum hemagglutination was found positive in 137 patients and negative in two patients. Hence, 137 patients were confirmed syphilis cases, constituting 4.36% of total STD cases in our STI clinic in 4 years. Out of 137 patients, 2 (1.45%) presented with primary chancre, 6 (4.37%) with lesions of secondary syphilis and 129 (94.16%) were found serologically reactive without any symptoms or clinical signs, i.e., in latent syphilis. Our records also showed 14 (10.21%) cases of HIV and syphilis co-infection. Conclusion: In our study, a remarkable rise in the number of patients in the latent syphilis stage is observed over primary and secondary syphilis stage. This signifies the persistence of syphilis in subclinical phase in the community and unfortunately, it goes unnoticed. These could be "warning signs" for changing disease pattern of syphilis in India and points toward hidden resurgence of syphilis as being reported in various parts of the world. To actively look for these "hidden cases," there is a need to strengthen "Suraksha clinics." VDRL testing should be mandatory along with routine testing in all patients visiting the hospital irrespective of their disease. We also propose for the central registration of syphilis patients on lines of HIV-infected patients' registry.

Nano-formulations in treatment of iron deficiency anaemia: An overview.

BACKGROUND: Iron deficiency anaemia (IDA) is a significant challenge to global health. The absorption and bioavailability depend on the delivery vehicle being used. Ferrous sulphate is a drug of choice for IDA but leads to frequent gastrointestinal tract side effects that force the patient to discontinue the treatment. Gastrointestinal side effects result from converting bivalent iron into trivalent iron accompanied by reactive oxygen species (ROS) formation. Due to lower absorption, oral preparations of trivalent iron are recommended in patients with intolerance to ferrous sulphate. Nanosized iron preparation can resolved these concerns. The particle size of iron salts has been observed to have a significant impact on iron absorption. The surface area of iron compounds is increased by reducing their particle size, which improves their solubility in gastric juice and boosts their absorption. Sucrosomial iron, ferric citrate complexes, and ferric maltol are some of the novel iron preparations that ensure high bioavailability and good tolerance in chronic kidney disease, congestive heart failure, and inflammatory bowel disease. However, the parenteral route of administration of iron is unacceptable to most patients. Moreover, it leads to high free iron levels in circulation, resulting in ROS generation. CONCLUSION: This article provides an informative summary of iron deficiency anaemia causes and treatment through nanoformulations and literature and in-depth patent analysis.

Increased Predisposition of SJS TEN in COVID-19 Patients, Presenting as Post COVID Complication: Report of Two Cases.

We report two consecutive cases of toxic epidermal necrolysis presented to our emergency department in the past 5 months. Both patients had history of fever prior to the onset of skin manifestations and showed radiological findings suggestive of COVID-19 pneumonia and elevated D dimers. ALDEN score was used to assess the drug causality, which showed probable and possible associations, respectively. In this report, along with brief review of literature, we highlight the possible role of viral etiology, that is SARS-Cov2, in triggering toxic epidermal necrolysis.

Vulval dermatoses (venereal and nonvenereal) among female patients presenting to a tertiary care hospital in North India.

Background: The skin and mucosa of the vulva are different from the rest of the human body, as it is derived from all three embryological layers. It is more prone to dermatological diseases, both infectious and noninfectious. Aims and Objectives: Our study was a prospective descriptive study on female patients attending the skin outpatient department with complaints of vulval dermatoses. Our aim was to determine the prevalence of venereal and nonvenereal dermatoses (infectious and non-infectious) along with age-wise distribution of these in our area. Materials and Methods: All female patients presenting with visible skin lesions on the vulva from January 2019 to December 2019 were included in this study. Various diagnostic tests such as Gram staining, Tzanck smear, KOH mount, herpes simplex virus serology, and skin biopsy were performed wherever necessary. Observations and Results: The study included 520 patients in whom 525 lesions were identified. These were grouped under venereal and non-venereal dermatoses. Nonvenereal dermatoses were further grouped under infectious and non-infectious conditions. Maximum patients were in the age group of 21-40 years (50.19%). The most common dermatoses were non-venereal infections, seen in 220 (42.30%) patients followed by non-venereal, non-infectious dermatoses seen in 177 (34.04%) patients whereas venereal dermatoses were seen in 128 (24.61%) patients. Conclusion: Most of the patients were in the reproductive age group, and the prevalence of infectious dermatoses both venereal and non-venereal was much more than that of non-infectious conditions affecting the vulval skin as per our study.

Skin as a Mirror to Internal Malignancy: A Rare Co-presentation of Nail Bed Squamous Cell Carcinoma and Renal Cell Carcinoma.

Squamous cell carcinoma (SCC) of the nail bed is not encountered commonly although it is the most common primary malignancy at this site. In general, it has a low rate of spread, except for high risk types which carry a greater risk of spread. Screening for systemic tumours should be done in all cases especially in the elderly. We present the case of a 67 year old male who was otherwise healthy and presented with just nail discoloration associated with pain and occasional profuse bleeding with minor trauma which turned out to be SCC of nail bed on biopsy. Subsequently, he was screened for internal malignancies and was found to have clear cell Renal cell carcinoma of right kidney and a metastatic nodule in right lung. This presentation has not been previously described in literature.

Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study.

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential -16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.

Changing trends of sexually transmitted infections and estimation of partner notification at a tertiary care center in North India.

BACKGROUND: Sexually transmitted infections (STIs) are dynamic and show a variable prevalence in different parts of the country. Moreover, the prevalence changes with time in the same geographical area. It is important to have the knowledge of current trend of STIs and partner notification (PN) rate in a particular area for the effective implementation of preventive and control measures. AIMS: This study aimed to assess the changing demographic and clinical trends of STIs in the patients attending a tertiary care center in North India. MATERIALS AND METHODS: This study was conducted at STI clinic located at a tertiary care center in North India. All the patients visiting STI clinic over a 5-year period from January 1, 2013, to December 31, 2017, were included in our study. Diseases were diagnosed on the basis of detailed history, clinical examination, and relevant investigations, and PN was done using the patient-oriented notification method. RESULTS: The most common STI affected age group was 25-44 years (45.11%), and the most common STI noted was candidal balanoposthitis in males (19.49%) and candidal vaginal discharge in females (20.54%), followed by herpes genitalis (15.04%) and condylomata acuminata (14.66%) in both the genders. Bacterial STIs such as syphilis (1.58%), lymphogranuloma venereum (0.45%), and chancroid (0.39%) were less common. The average PN rate was 42.48%. CONCLUSION: In the present study, fungal and viral STIs showed an upward trend, whereas bacterial STIs such as syphilis and chancroid demonstrated a declining trend. The measures to improve PN are urgently required for both cure and the prevention of STIs.

Metal-plant frameworks in nanotechnology: An overview.

BACKGROUND: Since ancient times, potential of plants in research and medicine have found pronounced applications, due to better therapeutic value. To meet the mounting demands for commercial nanoparticles, novel eco-friendly methods of synthesis has led to a remarkable progress via unfolding a green synthesis protocol towards metallic nanoparticles synthesis. HYPOTHESIS/PURPOSE: This review highlights the biological synthesis of various metallic nanoparticles as safe, cost effective process, where the phytochemicals present in extract such as flavonoid, phenols, terpenoids act as capping, reducing and stabilizing agents. Moreover, due to their nano size, the nanoparticles directly bind to bacterial strains leading to higher antimicrobial activity. CONCLUSION: Nano-sized dosage systems have a potential for enhancing the activity and overcoming problems associated with phyto medicines. Hence, synthesis of metallic nanoparticles using various plant extracts, emerge as safe alternative to conventional methods for biomedical applications.

Optimization of reaction conditions to fabricate Ocimum sanctum synthesized silver nanoparticles and its application to nano-gel systems for burn wounds.

The present study deals with sequential optimization strategy based on Box-Behnken method to optimize the process variables for efficient production of Ocimum sanctum synthesized silver nanoparticles using biological synthesis. Four substantial factors influencing the dependent variables viz size, zeta potential, Polydispersity index (PDI) and yield were identified as silver nitrate concentration, temperature, amount of plant extract and stirring speed as independent variables. The contribution of the studied factors in monitoring dependent variables was evaluated via analysis of variance. The validity of the model developed was verified, and the statistical analysis showed that the optimal operational conditions were AgNO3 concentration 5.29 mM, temperature 60 °C, agitation speed of 500 rpm and plant extract 2.24% (w/v) which primes to form silver nanoparticles of smallest size 83.41 nm and 0.24 with maximum zeta potential of -20.20mV and Yield of 18.62. In addition, the optimized AgNPs were characterized using DLS, TEM, FE-SEM and UV-vis analysis. The topical formulation was prepared by incorporation of optimized AgNPs into the carbopol gel base. Further, the gel was evaluated in vivo using the rat model of skin wound healing. The measurement of the wound areas was performed on 2nd, 4th, 6th, 8th, 10th, 12th and 14th days and the percentage of wound closures were calculated accordingly. By the 14th day, silver nanoparticle gel showed 96.20% wound healing activity compared with that of the standard as well as control base. The antibacterial inhibitory efficiency of prepared nano gel was found similar to the commercial product against the Staphylococcus aureus, E. coli and Pseudomonas aeruginosa.

A study of clinicopathological correlation of pruritic papular eruptions in HIV patients.

CONTEXT: Pruritic papular eruption (PPE) is a chronic eruption of papular and pruritic lesions of unknown etiology, symmetrically distributed over trunk and extremities. These are common cutaneous manifestations in HIV patients. It is an important cause of HIV-related morbidity. PPE can be the first marker of HIV. Their etiology, histopathological findings, and associated factors vary from region to region. There are no clear data available on the etiology, exact spectrum of the condition, histopathological findings, or treatment of PPE. AIMS: The study is aimed at documenting the etiology, CD4 count, and its histopathological correlation in HIV-infected patients. SETTINGS AND DESIGN: An observational study conducted in Government Medical College, Patiala. SUBJECTS AND METHODS: Two-year data regarding history, HIV status, cluster of differentiation 4 (CD4) cell count, and skin biopsy of clinically suspected PPE patients with known HIV status were analyzed. STATISTICAL ANALYSIS USED: All the results were then statistically analyzed. Categorical data were analyzed by Chi-square test, and one-way Spearman's rho test was used for multiple group comparison. RESULTS: Data of 50 eligible patients were analyzed. The majority of the patients were female (between 21 and 50 years of age). The most common histopathological patterns were of papular urticaria, scabies, and drug reaction, and the others less common PPE were polymorphic light eruption and eosinophilic folliculitis. Patients with papular urticaria (32%) had significantly lower mean CD4 counts (157 cells/mm3), while in scabies, the mean CD4 count (376 cells/mm3) was higher. CONCLUSIONS: We conclude that histopathology helps in specifying the pattern of PPE and its etiology. It can be a marker of advanced HIV infection. Thus, correlation between the histopathology, clinical diagnosis, and CD4 counts helps to know the disease process.

Eruptive pseudoangiomatosis - cherry angiomas with perilesional halo.

Eruptive pseudoangiomatosis is a rare viral exanthem characterized by acute onset of hemangiomata-like lesions, however, histological findings are distinct from that of true angiomas. This entity has been reported from Europe, North America, Japan, and Korea till date. Here, we report 12 cases of eruptive pseudoangiomatosis from a tertiary care hospital in Punjab.

Association of genetic polymorphism of interleukin-17A & interleukin-17F with susceptibility of psoriasis.

BACKGROUND & OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population. METHODS: A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis. RESULTS: Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls. INTERPRETATION & CONCLUSIONS: The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.