Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

Targeted Delivery of Natural Bioactives and Lipid-nanocargos against Signaling Pathways Involved in Skin Cancer.

At present, skin cancer is considered a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone to this malignancy in comparison to darker skin populations due to the lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is further categorized as basal and squamous cell carcinoma. Exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors to skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAK-STAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic limitations. Thus, many phytochemicals have been evaluated either alone or in combination with the existing synthetic drugs to overcome their limitations and have been found to play a promising role in the prevention and treatment. In this review, a complete overview of skin cancer, starting from the signaling pathways involved, newer developed drugs with their targets and limitations, along with the emerging role of natural products alone or in combination as potent anticancer agents and their molecular mechanism involved has been discussed. Apart from this, various nano-cargos have also been mentioned here, which can play a significant role in the management and treatment of different types of skin cancer.

Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer.

The objective of this investigation was to develop dual drug-loaded nanostructured lipid carrier (NLC) gel of quercetin and resveratrol to enhance their disposition in dermal and epidermal layers. The optimization of the lipidic phase, i.e., liquid lipid and solid lipid was done on the basis of the solubility of quercetin & resveratrol in lipids in the preformulation stage. NLC formulation was optimized by central composite rotatable design (CCRD). The NLC formulation contained lipid binary mixture (1.0% w/w) and Cremophor RH40 (5% w/v) as a surfactant and had a particle size of 191 nm ± 5.20, polydispersity index (PDI) of 0.33 ± 0.01, zeta potential (ZP) of -10.00 mV ± 0.30 and entrapment efficiency (EE) of 92.85 ± 0.25% (quercetin), 89.05 ± 0.18% (resveratrol) respectively. The flux and permeability coefficient of quercetin and resveratrol from NLC gel were found to be 14.09 µg/cm2/h, 3.70 µg/cm2/h and 7.21 × 10-2 cm/h, 4.69 × 10-2 cm/h respectively. Dermatokinetic studies revealed that there was a significant increase in the CSkin max and AUC0-8 h in skin treated with NLC gel as compared to skin treated with conventional gel, which was prepared using carbopol 934 (1.5% w/w). Further, all claims of dermatokinetic studies were proved by confocal microscopic (CLMS) studies, which revealed that the disposition of combinatorial NLC gel was higher (~3 folds) as compared to the conventional gel. Furthermore, skin treated with NLC gel and untreated skin were analysed by FTIR and DSC spectra to understand the permeation dynamics of NLC gel. The cytotoxic effect of combinatorial NLC gel and the conventional gel assessed in human epidermoid carcinoma (A431) cell line by MTT assay, revealed that IC50 of NLC gel and the conventional gel was 86.50 µM and 123.64 µM respectively. Thus, these results disclosed that NLC gel could be used as a potential carrier for the delivery of quercetin & resveratrol into deeper layers of the skin and can serve as a promising formulation for treatment of skin cancer.

Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting.

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

Trends in nanotechnology-based delivery systems for dermal targeting of drugs: an enticing approach to offset psoriasis.

INTRODUCTION: Psoriasis is identified as an inflammatory, chronic, auto-immune disease requiring long-term treatment, imposing an unnecessary burden on the patient. A significant impediment for the treatment of dermatological disorders via transdermal route is the inability of drug molecules to cross the stratum corneum (SC), as the larger size of drug molecules inhibits them to pervade into the skin, thus hampering their absorption. Some drugs exhibit systemic side-effects, which curbs patient compliance, resulting in treatment discontinuation. AREAS COVERED: This review aims to describe the detailed study such as demographic status, molecular factors of psoriasis, treatment with emerging combination therapy and role of nanotechnology tools in the treatment of psoriasis. EXPERT OPINION: To overcome problems related to the conventional drug delivery system, several nanotechnology-based formulations have been devised to enhance bioavailability, drug permeation and accumulation in the skin. Nano-formulations provide better permeation, targeted delivery and enhanced efficacy, thus gaining enormous popularity for cutaneous disorders. This pervasive review provides an overview of the pathophysiology of the disease, its molecular targets and the available herbal, synthetic and combination treatment modalities. The review also systematizes recent works utilizing nano-carriers to improve the treatment denouement of psoriasis.

Drosophila Choline transporter non-canonically regulates pupal eclosion and NMJ integrity through a neuronal subset of mushroom body.

Insect mushroom bodies (MB) have an ensemble of synaptic connections well-studied for their role in experience-dependent learning and several higher cognitive functions. MB requires neurotransmission for an efficient flow of information across synapses with different flexibility to meet the demand of the dynamically changing environment of an insect. Neurotransmitter transporters coordinate appropriate changes for an efficient neurotransmission at the synapse. Till date, there is no transporter reported for any of the previously known neurotransmitters in the intrinsic neurons of MB. In this study, we report a highly enriched expression of Choline Transporter (ChT) in Drosophila MB. We demonstrate that knockdown of ChT in a sub-type of MB neurons called α/ß core (α/ßc) and ϒ neurons leads to eclosion failure, peristaltic defect in larvae, and altered NMJ phenotype. These defects were neither observed on knockdown of proteins of the cholinergic locus in α/ßc and ϒ neurons nor by knockdown of ChT in cholinergic neurons. Thus, our study provides insights into non-canonical roles of ChT in MB.

Discordant interpretation of serial bone mineral density measurements by dual-energy X-ray absorptiometry using vendor's and institutional least significant changes: Serious impact on decision-making.

Meaningful change in bone mineral density (BMD) should be equal or higher than institutional least significant change (LSC). But some facilities use vendor's LSC which is discouraged by International Society for Clinical Densitometry (ISCD). The aim of this study was to find the impact of scan interpretation upon interval BMD changes using vendors and institutional LSCs. This prospective study was conducted at Joint Commission International-accredited facility of Pakistan from April-June 2017 using Hologic Discovery-A scanner. As per ISCD recommendations, precision error and LSC of two technologists were measured. Serial BMD changes such as deterioration or improvement interpreted based on vendor's and institutional LSCs were compared. Serial BMD changes in 102 patients were included, having a mean age, male:female ratio, and mean body mass index of 63 years, 94%:06%, and 29.274 kg/m2, respectively. Mean menopausal age was 47 years and mean duration between two dual X-ray absorptiometry (DXA) studies was 3 years. BMD changes over hip were found significant in 55% and 53% cases against vendor's and institutional LSCs, respectively (nonsignificant discordance in 2%). BMD changes using vendor's and institutional LSCs were found significant over L1-4 (62% vs. 46%; discordance: 14%) and distal forearm (77% vs. 35%; discordance: 41%), respectively. Interpretations based on vendor's LSCs revealed significantly overestimated deterioration over forearm and improvement over L1-4 BMD values. We conclude that vendor's provided LSC for interpretation of serial DXA is misleading and has a significant negative impact upon patients' management. Every DXA facility must use its own LSC as per ISCD guidelines. Furthermore, ISCD must consider publishing cutoff values for LSC for distal forearm measurement.

Effects of methanolic and aqueous extracts of Ipomoea batatas L on mineral contents level (calcium and magnesium) in alloxan-induced diabetic rats.

In diabetic patients, electrolyte disorders frequently occur with the characteristic changes in minerals like calcium and magnesium etc. Several medicines are used to manage diabetes mellitus but they exert adverse effects. Plants are a valuable alternative to synthetic medicines because they are easily available, economical and have fewer side effects. Ipomoea batatas L is a well-known antidiabetic plant (sweet potato) but its effects on calcium and magnesium concentration have not studied. The prime focus of this study is to estimate the potential of Ipomoea batatas L peel-off on magnesium and calcium level in Alloxan-induced diabetic rats. Alloxan monohydrate was mixed in 0.9% NaCl solution and administrated [150 mg/kg (S/C)] to male Wistar rats to induce diabetes. After three days blood samples were collected and blood glucose level was recorded. Wistar rats having a blood glucose level of 200 mg/dl and above were selected for the study. Methanol and water extract of Ipomoea batatas L peel-off was given orally with a dose rate of 4g/day. Calcium and magnesium estimation was done using an atomic absorption spectrophotometer. Our results revealed an increase in both the calcium and magnesium level in heart, brain, liver, hind limb, and forelimb after Ipomoea batatas extract treatment. In kidneys decreased calcium level was noted as they excrete calcium. Mineral (Calcium, magnesium) level was increased in all organs except kidney after both extracts treatment. Ipomoea batatas being anti-diabetic in nature also maintain the homeostasis of calcium and magnesium in diabetes. Therefore, we propose the long-term use of such agents might help in the prevention of diabetes-associated complications. However, the validation of these results to human population needs further extensive study.

Diagnostic accuracy study of internal assessment using receiver operator characteristic curve analysis.

OBJECTIVE: To assess whether internal assessment as a part of continuous assessment links to the outcome of the final summative assessment. METHODS: The diagnostic accuracy study was conducted at Army Medical College, Rawalpindi, Pakistan, from November 2015 to July 2016, and comprised medical students of 2nd year. Different teaching methods used were interactive lectures, case-based sessions, demonstrations, small group discussions, skill lab and practicals. Other confounding factors were not considered. Receiver operator characteristic curve was computed to determine diagnostic accuracy of internal assessment for the prediction of examination results.. RESULTS: Out of 202 students, 122 (60.4%) were male and 80 (39.6%) were female with an overall mean age of 20.05±0.69 years. Total marks of 2nd professional examination and internal assessment were normally distributed with mean values of 131.71±19.81 and 36.18±8.03 respectively. The cut-off value was 27.5 and at this value, sensitivity was 100% and specificity was 91%. CONCLUSIONS: Diagnostic power of internal assessment to identify students who may fail in professional examination was significantly high.

Acidic and enzymatic saccharification of waste agricultural biomass for biotechnological production of xylitol.

BACKGROUND: The plant biomass and agro-industrial wastes show great potential for their use as attractive low cost substrates in biotechnological processes. Wheat straw and corn cob as hemicellulosic substrates were acid hydrolyzed and enzymatically saccharified for high xylose production. The hydrolysate was concentrated and fermented by using Saccharomyces cerevisiae and Kluyveromyces for production of xylitol. RESULTS: Acid hydrolysis of wheat straw and corn cob in combination with enzymatic hydrolysis showed great potential for production of free sugars from these substrates. Kluyveromyces produced maximum xylitol from acid treated wheat straw residues with enzymatic saccharification. The percentage xylitol yield was 89.807 g/L and volumetric productivity of 0.019 g/L/h. Kluyveromyces also produced maximum xylitol from corn cob acid hydrolyzed liquor with xylitol yield 87.716 g/L and volumetric productivity 0.018 g/L/h. CONCLUSION: Plant and agro-industrial biomass can be used as a carbohydrate source for the production of xylitol and ethanol after microbial fermentation. This study revealed that wheat straw acid and enzyme hydrolyzed residue proved to be best raw material for production of xylitol with S. cerevisiae. The xylitol produced can be utilized in pharmaceuticals after purification on industrial scale as pharmaceutical purposes.

Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen.

Interindividual variability in polymorphic uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) ascribed to genetic diversity is associated with relative glucuronidation level among individuals. The present research was aimed to study the effect of 2 important single nucleotide polymorphisms (SNPs; rs8330 and rs10929303) of UGT1A1 gene on glucuronidation status of acetaminophen in healthy volunteers (n = 109). Among enrolled volunteers, 54.13% were male (n = 59) and 45.87% were female (n = 50). The in vivo activity of UGT1A1 was investigated by high-performance liquid chromatography-based analysis of glucuronidation status (ie, acetaminophen and acetaminophen glucuronide) in human volunteers after oral intake of a single dose (1000 mg) of acetaminophen. The TaqMan SNP genotyping assay was used for UGT1A1 genotyping. The wild-type genotype (C/C) was observed the most frequent one for both SNPs (rs8330 and rs10929303) and associated with fast glucuronidator phenotypes. The distribution of variant genotype (G/G) for SNP rs8330 was observed in 5% of male and 8% of the female population; however, for SNP rs10929303, the G/G genotype was found in 8% of both genders. A trimodal distribution (fast, intermediate, and slow) based on phenotypes was observed. Among the male participants, the glucuronidation phenotypes were observed as 7% slow, 37% intermediate, and 56% fast glucuronidators; however, these findings for the females were slightly different as 8%, 32%, and 60% respectively. The k-statistics revealed a compelling evidence for good concordance between phenotype and genotype with a k value of 1.00 for SNP rs8330 and 0.966 for SNP rs10929303 in our population.

Chemical Composition and in-Vitro Evaluation of the Antimicrobial and Antioxidant Activities of Essential Oils Extracted from Seven Eucalyptus Species.

Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan). EOs from Eucalyptus citriodora, Eucalyptus melanophloia, Eucalyptus crebra, Eucalyptus tereticornis, Eucalyptus globulus, Eucalyptus camaldulensis and Eucalyptus microtheca were extracted from leaves through hydrodistillation. The chemical composition of the EOs was determined through GC-MS-FID analysis. The study revealed presence of 31 compounds in E. citriodora and E. melanophloia, 27 compounds in E. crebra, 24 compounds in E. tereticornis, 10 compounds in E. globulus, 13 compounds in E. camaldulensis and 12 compounds in E. microtheca. 1,8-Cineole (56.5%), α-pinene (31.4%), citrinyl acetate (13.3%), eugenol (11.8%) and terpenene-4-ol (10.2%) were the highest principal components in these EOs. E. citriodora exhibited the highest antimicrobial activity against the five microbial species tested (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Rhizopus solani). Gram positive bacteria were found more sensitive than Gram negative bacteria to all EOs. The diphenyl-1-picrylhydazyl (DPPH) radical scavenging activity and percentage inhibition of linoleic acid oxidation were highest in E. citriodora (82.1% and 83.8%, respectively) followed by E. camaldulensis (81.9% and 83.3%, respectively). The great variation in chemical composition of EOs from Eucalyptus, highlight its potential for medicinal and nutraceutical applications.