Understanding the role of hyperglycemia and the molecular mechanism associated with diabetic neuropathy and possible therapeutic strategies.

Diabetic neuropathy is a neuro-degenerative disorder that encompasses numerous factors that impact peripheral nerves in the context of diabetes mellitus (DM). Diabetic peripheral neuropathy (DPN) is very prevalent and impacts 50% of diabetic patients. DPN is a length-dependent peripheral nerve lesion that primarily causes distal sensory loss, discomfort, and foot ulceration that may lead to amputation. The pathophysiology is yet to be fully understood, but current literature on the pathophysiology of DPN revolves around understanding various signaling cascades involving the polyol, hexosamine, protein-kinase C, AGE, oxidative stress, and poly (ADP ribose) polymerase pathways. The results of research have suggested that hyperglycemia target Schwann cells and in severe cases, demyelination resulting in central and peripheral sensitization is evident in diabetic patients. Various diagnostic approaches are available, but detection at an early stage remains a challenge. Traditional analgesics and opioids that can be used "as required" have not been the mainstay of treatment thus far. Instead, anticonvulsants and antidepressants that must be taken routinely over time have been the most common treatments. For now, prolonging life and preserving the quality of life are the ultimate goals of diabetes treatment. Furthermore, the rising prevalence of DPN has substantial consequences for occupational therapy because such therapy is necessary for supporting wellness, warding off other chronic-diseases, and avoiding the development of a disability; this is accomplished by engaging in fulfilling activities like yoga, meditation, and physical exercise. Therefore, occupational therapy, along with palliative therapy, may prove to be crucial in halting the onset of neuropathic-symptoms and in lessening those symptoms once they have occurred.

Feasibility of a Novel Video Game-Based Electromyography Biofeedback System in Patients With Knee Osteoarthritis.

CONTEXT: A novel virtual game system Knee Biofeedback Rehabilitation Interface for game-based home therapy (KneeBright) was developed for strength training using integrated electromyography biofeedback of the quadriceps muscle to control the game. The study aimed to compare the KneeBright and electromyography biofeedback interface among patients with knee osteoarthritis. DESIGN: Controlled before and after design. METHODS: Nineteen patients with knee osteoarthritis took part in this laboratory-based study. Exercise sessions took place on 2 separate days. During session 1, participants used a conventional electromyography biofeedback system while performing 3 sets of lower body exercises with emphasis on maximal muscle activation, endurance, and precision. During session 2, participants used the KneeBright game to match the exercise sets in the first session. For both sessions, knee extension torque during the isometric muscle activation exercises and time to voluntary additional exercise were recorded. Patient engagement was assessed using the technology acceptance model and System Usability Score questionnaires. RESULTS: The peak knee extension torque produced during the control exercise session and the KneeBright exercise session were positively correlated. Knee extension torque generated during KneeBright game exercise sessions was increased by an average of 25% compared to the control sessions (2.14 vs 1.77 N·m/kg, P = .02). The mean technology acceptance model score for the KneeBright system was 3.4/5 and the mean System Usability Score was 79, both indicating positive patient engagement. CONCLUSIONS: Patients using the KneeBright game produced greater knee torque than patients using the conventional system, had positive levels of engagement, and exercised longer with the KneeBright game.

Parthenium hysterophorus mediated inflammation and hyper-responsiveness via NF-κB pathway in human A549 lung cancer cell line.

Being one of the notorious weed P. hysterophorus has invaded almost every part India and is the lead cause of skin allergies and severe dermatitis among farmers and rural population. It is an invasive obnoxious weed capable of surviving extreme environmental conditions and various parts of this plant are reported to cause severe contact allergies in humans due to the presence of high concentrations of toxic sesquiterpene lactones viz. parthenin. It can stimulate numerous cellular and immune responses that may translate into Oxidative stress, allergies, and inflammation. The effect of P. hysterophorus flower extract was evaluated on cell viability, oxidative stress and inflammation in A549 lung cancer cell line by spectrophotometric and reverse transcriptase-polymerase chain reaction methods. Schrodinger software based docking was performed for possible interactions studies. The A549 cells treated with P. hysterophorus flower extract favors increase in cell viability, reactive oxygen species generation. The mRNA expression of proinflammatory cytokines such as IFN-γ, TNF-α, and IL-1ß was significantly increased whereas no change in IL-18 expression was observed. Significant increase in protein expression of NF-κB was observed, suggesting the role of NF-κB signalling in allergic responses. The docking studies demonstrated the potential interaction between Parthenin and NF-κB/IL-1ß/IL-18 suggesting their activation leading to inflammation. The current study emphasize that P. hysterophorus mediates oxidative stress, and inflammatory process via alterations in expression of proinflammatory cytokines such as IL-1ß, IFN-γ through NF-κB activation which was also confirmed in docking studies. Cellular and molecular mechanisms involved in pathogenesis of allergic/chronic inflammation and severe dermatitis need to be further investigated to identify specific binding partners responsible for severe inflammation which can provide some leads in developing effective targets against severe dermatitis and skin allergies.

Role of Oral Enzymes in Post Operative Septoplasty Cases.

Enzymes are complex macromolecules of amino acids which biocatalyse various body processes. The aim of this study is to evaluate the effect of oral enzymes for control of infection and inflammation in post operative septoplasty cases. 40 patients planned for septoplasty under general anaesthesia were taken up for study. 20 patients were included in group E and were given a combination of oral enzymes postoperatively. Remaining 20 patients were included in group D and were given diclofenac and paracetamol combination postoperatively. Patients were evaluated post operatively after 1, 2 and 4 weeks for post operative pain , swelling , congestion , patient satisfaction and other criterias. The results showed that pain and swelling was significantly less in oral enzymes group . There was less nasal obstruction , discharge and more patient satisfaction in enzyme group. There were less complications in enzyme group. So it can be concluded that oral enzymes are more effective for control of infection and inflammation in post operative septoplasty cases.

Mining the deep Red-Sea brine pool microbial community for anticancer therapeutics.

BACKGROUND: Microbial species in the brine pools of the Red Sea and the brine pool-seawater interfaces are exposed to high temperature, high salinity, low oxygen levels and high concentrations of heavy metals. As adaptations to these harsh conditions require a large suite of secondary metabolites, these microbes have a huge potential as a source of novel anticancer molecules. METHODS: A total of 60 ethyl-acetate extracts of newly isolated strains from extreme environments of the Red-Sea were isolated and tested against several human cancer cell lines for potential cytotoxic and apoptotic activities. RESULTS: Isolates from the Erba brine-pool accounted for 50% of active bacterial extracts capable of inducing 30% or greater inhibition of cell growth. Among the 60 extracts screened, seven showed selectivity towards triple negative BT20 cells compared to normal fibroblasts. CONCLUSION: In this study, we identified several extracts able to induce caspase-dependent apoptosis in various cancer cell lines. Further investigations and isolation of the active compounds of these Red Sea brine pool microbes may offer a chemotherapeutic potential for cancers with limited treatment options.

Initiation, Switching, and Cessation of Psoriasis Treatments Among Patients with Moderate to Severe Psoriasis in the United States.

BACKGROUND: Psoriasis patients frequently switch among multiple therapies while managing their psoriasis. Determining treatment transitions is fundamental to understanding how patients access and use treatments. OBJECTIVE: We aimed to identify patterns of treatment transitions of US patients with moderate to severe psoriasis over 5 years. METHODS: This was a retrospective, longitudinal cohort study in which US patients aged ≥18 years who had at least one psoriasis claim (International Classification of Diseases, Ninth Revision [ICD-9] diagnosis) were continuously enrolled in a health plan between October 2007 and September 2012. Data from eligible patients were projected to reflect the total US insured population with moderate to severe psoriasis, and the proportions of patients who started, stopped, switched, and restarted treatment at any time between September 2011 and September 2012 were analyzed. Treatment categories were biologics, traditional oral systemics, topicals, phototherapy, lapsed from treatment, and treatment-naive. RESULTS: There were 8.9 million patients in the claims database, of whom 0.9 million (10.4%) had a psoriasis diagnosis and 46,369 (0.5%) met the inclusion criteria. When projected, 1.7 million insured patients had moderate to severe psoriasis. Of these, an estimated 807,000 patients had lapsed treatment, an additional 346,000 were receiving treatment, and 547,000 were defined as being treatment-naive. A total of 81,000 of 346,000 patients had switched treatment in the preceding year. In addition, many patients stopped (438,000) and restarted (384,000) treatment in the 12-month period. CONCLUSION: Based on health claims data, undertreatment of moderate to severe psoriasis appeared to be common.

Under-Treatment of Patients with Moderate to Severe Psoriasis in the United States: Analysis of Medication Usage with Health Plan Data.

INTRODUCTION: Psoriasis is a chronic inflammatory disorder with significant morbidity and mortality, but a persistent gap appears to exist for the adequate treatment of patients with moderate to severe disease. As the extent of under-treatment is unknown, we attempted to determine overall treatment patterns and estimate under-treatment using a large database. METHODS: Data from the US National Health and Wellness Survey was used to estimate the proportion of patients with mild, moderate or severe psoriasis. The proportion with moderate to severe disease was estimated by excluding those with mild disease, and projecting this to the total insured US population, weighted by age and gender. Using US health plan claims data, patient totals by treatment type were determined between October 1, 2007 and September 30, 2012. Patients had to be continuously enrolled in a health plan and be ≥18 years at the end of the analysis window. Psoriasis was confirmed if patients had at least one claim of any type of psoriasis except psoriatic arthropathy (ICD-9 code 696.1). A monthly treatment history, classified by biologic, traditional oral systemic, phototherapy and topical therapy, was recorded for each patient. RESULTS: There were an estimated 1.7 million insured US patients with moderate to severe psoriasis. Of these, 1 million (59%) were not treated for their condition in the preceding year. Among 695,488 patients who were treated for psoriasis in the preceding year, 346,201 were currently receiving treatment and 349,287 had lapsed treatment. Of the patients lapsed and currently treated in this period, the numbers who received each treatment type were 156,409 (biologic), 222,657 (traditional oral systemic), 22,911 (phototherapy), and 293,511 (topical). A limitation of the study was that only insurance claims were analyzed. CONCLUSION: Moderate to severe psoriasis remains persistently untreated or under-treated. We suggest that potential barriers preventing access to care be explored. FUNDING: This study was sponsored by Pfizer Inc.

The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives.

BACKGROUND: Psoriasis is a debilitating chronic inflammatory autoimmune disease affecting approximately 7.4 million adults in the United States. Plaque psoriasis is the most common form, affecting 80% to 90% of patients. OBJECTIVES: To describe the impact and challenges that psoriasis presents for various stakeholders, and to provide nondermatologist healthcare decision makers with information to enhance their contributions to drug and pharmacy benefit design discussions. DISCUSSION: Psoriasis carries an increased risk for early mortality and an increased prevalence of comorbidities, including psoriatic arthritis, cardiovascular disease, and diabetes. It is also associated with anxiety, depression, and social isolation, and can negatively impact patients' relationships, productivity, and careers. The physical, psychologic, social, and economic impact of psoriasis, plus the associated stigma, result in cumulative impairment over a patient's lifetime. The current treatments for moderate-to-severe psoriasis include topical therapy, phototherapy, and systemic drugs (nonbiologic and biologic); however, patient satisfaction remains low, combination therapy and treatment switching are common, and many patients remain untreated or undertreated. Clinicians should consider the patient holistically, and should select treatment based on a range of factors, including disease severity (with physical and psychosocial manifestations), susceptibility to cumulative life-course impairment (considering personality, behavior, and cognition), comorbidities, concomitant medication, and patient preference. It is estimated that the total annual direct cost of treating psoriasis in the United States in 2015 exceeded $12.2 billion. CONCLUSION: Psoriasis is a complex disease, and appropriate management is correspondingly complex. Newer psoriasis treatments provide improved efficacy and safety versus traditional treatments, but challenges remain in ensuring patients access to these medications. An improved understanding of the barriers to appropriate treatment is needed, as well as clear and accessible information for payers and clinicians on current treatment options, to ensure that decision makers can control costs while providing patients with optimal care.

A randomized, multicenter, double-blind, vehicle-controlled study evaluating the efficacy and safety of luliconazole cream 1% once daily for 7 days in patients aged ≥ 12 years with tinea cruris.

BACKGROUND: Tinea cruris, a pruritic superficial fungal infection of the groin, is the second most common clinical presentation for dermatophytosis. OBJECTIVE: This phase 3 study evaluated the safety and efficacy of topical luliconazole cream 1% in patients with tinea cruris. METHODS: 483 patients were enrolled and 256 male and female patients aged ≥12 years with clinically evident tinea cruris and eligible for modified intent-to-treat analysis were randomized 2:1 to receive luliconazole cream 1% (n=165) or vehicle (n=91) once daily for 7 days. Efficacy was evaluated at baseline and at days 7, 14, 21, and 28 based on mycology (potassium hydroxide, fungal culture) and clinical signs (erythema, scaling, pruritus). The primary outcome was complete clearance at day 28 (21 days posttreatment). Safety evaluations included adverse events and laboratory assessments. RESULTS: Complete clearance was obtained in 21.2% (35/165) of patients treated with luliconazole cream 1% compared with 4.4% (4/91) treated with vehicle (P<0.001). The safety profile of luliconazole cream 1% was similar to vehicle. LIMITATIONS: The study was conducted under controlled conditions in a relatively small population. CONCLUSION: Luliconazole cream 1% applied once daily for 7 days is more effective than vehicle and well tolerated in patients with tinea cruris.

Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts.

BACKGROUND: Marine microorganisms are considered to be an important source of bioactive molecules against various diseases and have great potential to increase the number of lead molecules in clinical trials. Progress in novel microbial culturing techniques as well as greater accessibility to unique oceanic habitats has placed the marine environment as a new frontier in the field of natural product drug discovery. METHODS: A total of 24 microbial extracts from deep-sea brine pools in the Red Sea have been evaluated for their anticancer potential against three human cancer cell lines. Downstream analysis of these six most potent extracts was done using various biological assays, such as Caspase-3/7 activity, mitochondrial membrane potential (MMP), PARP-1 cleavage and expression of γH2Ax, Caspase-8 and -9 using western blotting. RESULTS: In general, most of the microbial extracts were found to be cytotoxic against one or more cancer cell lines with cell line specific activities. Out of the 13 most active microbial extracts, six extracts were able to induce significantly higher apoptosis (>70%) in cancer cells. Mechanism level studies revealed that extracts from Chromohalobacter salexigens (P3-86A and P3-86B(2)) followed the sequence of events of apoptotic pathway involving MMP disruption, caspase-3/7 activity, caspase-8 cleavage, PARP-1 cleavage and Phosphatidylserine (PS) exposure, whereas another Chromohalobacter salexigens extract (K30) induced caspase-9 mediated apoptosis. The extracts from Halomonas meridiana (P3-37B), Chromohalobacter israelensis (K18) and Idiomarina loihiensis (P3-37C) were unable to induce any change in MMP in HeLa cancer cells, and thus suggested mitochondria-independent apoptosis induction. However, further detection of a PARP-1 cleavage product, and the observed changes in caspase-8 and -9 suggested the involvement of caspase-mediated apoptotic pathways. CONCLUSION: Altogether, the study offers novel findings regarding the anticancer potential of several halophilic bacterial species inhabiting the Red Sea (at the depth of 1500-2500 m), which constitute valuable candidates for further isolation and characterization of bioactive molecules.

Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea.

BACKGROUND: High salinity and temperature combined with presence of heavy metals and low oxygen renders deep-sea anoxic brines of the Red Sea as one of the most extreme environments on Earth. The ability to adapt and survive in these extreme environments makes inhabiting bacteria interesting candidates for the search of novel bioactive molecules. METHODS: Total 20 i.e. lipophilic (chloroform) and hydrophilic (70% ethanol) extracts of marine bacteria isolated from brine-seawater interface of the Red Sea were tested for cytotoxic and apoptotic activity against three human cancer cell lines, i.e. HeLa (cervical carcinoma), MCF-7 (Breast Adenocarcinoma) and DU145 (Prostate carcinoma). RESULTS: Among these, twelve extracts were found to be very active after 24 hours of treatment, which were further evaluated for their cytotoxic and apoptotic effects at 48 hr. The extracts from the isolates P1-37B and P3-37A (Halomonas) and P1-17B (Sulfitobacter) have been found to be the most potent against tested cancer cell lines. CONCLUSION: Overall, bacterial isolates from the Red Sea displayed promising results and can be explored further to find novel drug-like molecules. The cell line specific activity of the extracts may be attributed to the presence of different polarity compounds or the cancer type i.e. biological differences in cell lines and different mechanisms of action of programmed cell death prevalent in different cancer cell lines.

Use of immobilized Pseudomonas sp. as whole cell catalyst for the transesterification of used cotton seed oil.

Lipase enzyme producing bacteria, Pseudomonas sp., have been grown at varying oil concentrations to make it adaptive for high oil concentrations and it was found to show the maximum growth and maximum lipase activity when 40- and 30-vol% of oil respectively was used as a source of carbon in growth medium. Bacteria was immobilized with sodium alginate and used as whole cell catalyst for the transesterification of used cotton seed oil. Preliminary experiments resulted about 70% transesterification of used cotton seed oil with methanol as calculated by proton NMR technique.

Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism.

"Ethnopharmacological" use of roots of Boerhaavia diffusa (B. diffusa) in the treatment of epilepsy in Nigerian folk medicine and reports showing the presence of a calcium channel antagonistic compound "liriodendrin" in its roots, led us to undertake the present study. The study was designed to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. Air-dried roots of B. diffusa were extracted with methanol by cold maceration. The methanol soluble fraction of extract thus obtained was successively extracted to obtain liriodendrin-rich fraction and two side fractions, that is, chloroform fraction and phenolic compound fraction. Anti-convulsant activity of methanolic extract (1000, 1500 and 2000 mg kg(-1), intraperitoneally (i.p.)) and its different fractions, that is, liriodendrin-rich fraction (10, 20 and 40 mg kg(-1), i.p., chloroform fraction (20 mg kg(-1), i.p.) and phenolic compound fraction (1 mg kg(-1), i.p.) were studied in pentylenetetrazol (PTZ)-induced seizures (75 mg kg(-1), i.p.). The crude methanolic extract of B. diffusa and only its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions. The liriodendrin-rich fraction also showed significant protection against seizures induced by BAY k-8644. These findings reiterated the anti-convulsant activity of methanolic extract of B. diffusa roots. Furthermore, it can be concluded that the observed anti-convulsant activity was due to its calcium channel antagonistic action as this activity was retained only in the liodendrin-rich fraction, which has additionally been confirmed by significant anti-convulsant activity of liriodendrin-rich fraction in BAY k-8644-induced seizures.

Evaluation of an onion extract, Centella asiatica, and hyaluronic acid cream in the appearance of striae rubra.

This study evaluated the effect of an onion extract cream with Centella asiatica and hyaluronic acid in improving the appearance of striae rubra (SR). Women participants with bilateral, outer aspect of the thigh SR were randomized to apply a quarter-sized amount of the onion extract cream twice daily for 12 weeks to the randomized left or right, outer aspect of the thigh. No treatment was administered to the contralateral side. Participants were evaluated at weeks 2, 4, 8, and 12. Primary efficacy endpoints included color, texture, softness, and overall appearance of SR by the participant and investigator at week 12. The treated thigh demonstrated a statistically significant difference in the mean change in participant and investigator evaluations in overall appearance, texture, color, and softness compared with the untreated thigh at week 12. No adverse events occurred during the study. The onion extract cream was well tolerated and significantly improved the appearance of SR in women.

Pilot study of the effect of ultraviolet light on pain and mood in fibromyalgia syndrome.

BACKGROUND: There is a lack of effective systemic or adequate symptomatic treatment for pain associated with fibromyalgia syndrome (FMS). Anecdotes suggest ultraviolet (UV) light may be of some benefit. PURPOSE: The purpose of the present study was to determine if UV is effective in ameliorating chronic pain in persons with FMS. METHODS: Nineteen subjects with FMS were enrolled in a controlled trial of UV and non-UV (control) tanning beds for 2 weeks, followed by randomization to receive UV or non-UV (control) exposure for 6 additional weeks. A follow-up interview was conducted 4 weeks after the last treatment. Pain was assessed with an 11-point numerical pain rating (Likert scale), a visual analogue pain scale (VAS), and the McGill Pain Questionnaire. Mood variables were also assessed. RESULTS: During the initial 2 weeks when subjects received both UV and non-UV (control) exposures, the 11-point Likert scale pain score decreased 0.44 points after exposure to UV from pre-exposure levels (S.E. = .095). Additionally, UV exposure resulted in greater positive affect, well-being, relaxation, and reduced pain levels when compared to non-UV (control) exposure (Odds Ratio [OR] = 2.80, p = 0.0059). Following the randomized treatment period, there was slight improvement in pain as measured by the McGill Pain Questionnaire in the UV group compared to the non-UV (control) group (12.2 versus 14.1; p = 0.049); the other pain scales yielded nonsignificant results. Assessment 4 weeks after the last treatment showed no significant differences in scores in the adjusted means for outcomes. CONCLUSIONS: Results from this pilot study suggest that tanning beds may have some potential in reducing pain in persons with FMS.

Nonlaser UVB-targeted phototherapy treatment of psoriasis.

Nonlaser localized narrowband (290-315 nm) UVB phototherapy was tested in 10 subjects with localized psoriasis. Treatments were given 2 to 3 times weekly. Four patients did not complete the planned 25-treatment course. Of the remaining 6 patients, all reached greater than 90% clearing of their disease. Localized nonlaser UVB phototherapy is another option for the treatment of localized psoriasis.