Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable Long-Acting Insulin in a Rodent Model of Diabetes Eye Disease.

Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize that a combination therapy targeting inflammation and hyperglycemia can prevent diabetic eye diseases. Here, we report a multipronged approach to prevent diabetic cataracts and retinopathy by combining orally bioavailable curcumin-laden double-headed (two molecules of gambogic acid conjugated to terminal carboxyl groups of poly(d,l-lactide-co-glycolide)) nanoparticles and injectable basal insulin. The combination treatment led to a significant delay in the progression of diabetic cataracts and retinopathy, improving liver function and peripheral glucose homeostasis. We found a concurrent reduction in lens aggregate protein, AGEs, and increased mitochondrial ATP production. Importantly, inhibition of Piezo1 protected against hyperglycemia-induced retinal vascular damage suggesting possible involvement of Piezo1 in the regulation of retinal phototransduction. Histologic evaluation of murine small intestines revealed that chronic administration of curcumin-laden double-headed nanoparticles was well tolerated, circumventing the fear of nanoparticle toxicity. These findings establish the potential of anti-inflammatory and anti-hyperglycemic combination therapy for the prevention of diabetic cataracts and retinopathy.

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation.

Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)-coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA2-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles (n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) (n = 8) and untreated controls (n = 8). PLGA-GA2-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA2 nanoparticles for systemic drug delivery across ocular barriers.

Strength training for partially paralysed muscles in people with recent spinal cord injury: a within-participant randomised controlled trial.

STUDY DESIGN: Within-participant randomised controlled trial. OBJECTIVES: To determine whether strength training combined with usual care increases strength in partially paralysed muscles of people with recent spinal cord injury (SCI) more than usual care alone. SETTINGS: SCI units in Australia and India. METHODS: Thirty people with recent SCI undergoing inpatient rehabilitation participated in this 12-week trial. One of the following muscle groups was selected as the target muscle group for each participant: the elbow flexors, elbow extensors, knee flexors or knee extensors. The target muscle on one side of the body was randomly allocated to the experimental group and the same muscle on the other side of the body was allocated to the control group. Strength training was administered to the experimental muscle but not to the control muscle. Participants were assessed at baseline and 12 weeks later. The primary outcome was maximal isometric muscle strength, and the secondary outcomes were spasticity, fatigue and participants' perception of function and strength. RESULTS: There were no dropouts, and participants received 98% of the training sessions. The mean (95% confidence interval (CI)) between-group difference for isometric strength was 4.3 Nm (1.9-6.8) with a clinically meaningful treatment effect of 2.7 Nm. The mean (95% CI) between-group difference for spasticity was 0.03/5 points (-0.25 to 0.32). CONCLUSION: Strength training increases strength in partially paralysed muscles of people with recent SCI, although it is not clear whether the size of the treatment effect is clinically meaningful. Strength training has no deleterious effects on spasticity.

Successful treatment of mild to moderate acne vulgaris with Dr Michaels® (also branded as Zitinex®) topical products family: a clinical trial.

Acne vulgaris is an epidemic inflammatory skin disease of multi-factorial origin, frequently seen in adolescents and often persisting or occurring through to adulthood. Acne vulgaris is a nearly universal skin disease afflicting 79-95% of the adolescent population in westernized societies and is a significant cause of psychological morbidity in affected patients. Despite the various treatment options available for acne, there is still a need for a safe and effective option. The aim of the study was to investigate the efficacy and tolerability of Dr Michaels® (Zitinex®) product family in the treatment of papulo-pustular acne. 25 patients (17 female/8 male), aged 15-22, with a mild to moderate papulo-pustular acne, localized on the face and on the trunk, were included in this study. None of the patients had used any other kind of treatment in the 3 months prior to commencing this study. All of the patients were treated with Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, a cream, PSC 200 and PSC 900 oral supplements. Application time of Dr Michaels® (Zitinex®) products was 12 weeks. The treatment was been evaluated clinically at 0, 4, 8 and 12 weeks. All of the patients showed an improvement in all parameters of their acne (comedones, papules, pustules, hyperpigmentation and scars). The acne lesions and erythema had mostly resolved. The hyperpigmentation and pitted scarring had significantly reduced also, with the skin appearing smoother. The treatment was well tolerated and no side effects have been described. Our study demonstrates that the Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, cream and oral supplements PSC 200 and PSC 900 are an effective therapeutic option for the treatment of moderately severe acne vulgaris. Moreover, it highlights the safety profile of the Dr Michaels® (Zitinex®) product family in a case of acne compared to traditional first-line treatments.

Investigation of the efficacy and tolerability of Dr Michaels® (also branded as Eczitinex® and Itchinex Eczitinex®) topical products in the treatment of atopic dermatitis in children.

Atopic eczema is a chronic relapsing inflammatory skin disorder, characterized clinically by intensely pruritic eczematous skin lesions and a defective epidermal barrier. It affects more than 15% of children and up to 10%of adults, which makes the disease a social health problem still without a challenging treatment. The aim of this study was to evaluate the efficacy and tolerability of Dr Michaels® (Eczitinex®) topical product family in the treatment of atopic dermatitis in children. We studied a group of 30 patients (17 female, 13 male), aged 5 to 13 (mean age: 9), affected by atopic dermatitis since they were newborn. All patients had been unsuccessfully treated with conventional anti-inflammatory therapies and ceased treatment 2 weeks before commencing research. The patients were treated with Dr Michaels® (Eczitinex® and Itchinex®) product family including a moisturising bar, topical ointment and PSC 900 oral herbal formulation. The treatment was evaluated clinically and photographically at 0, 1, 2, 4, 6, 8, 10, 12, and 14 weeks. Twenty-eight patients showed a significant improvement of cutaneous rashes and pruritus on the first week of treatment, with a complete remission at 10-12 weeks. Only two patients, brother and sister respectively, showed a slow response to treatment and reported an increasing itching. Following 14 weeks of treatment with the Dr Michaels® (Eczitinex® and Itchinex®) product family, patients demonstrated complete resolution of their AD. All patients showed a marked improvement in their condition within 3 days of treatment with most of the lesions and symptoms totally resolved within 10 to 12 weeks of treatment with Dr Michaels® (Eczitinex® and Itchinex®) family of products. This clinical report highlights that the Dr Michaels® (Eczitinex® and Itchinex®) product family is a safe and effective treatment option for AD.

Successful treatment of recalcitrant candidal intertrigo with Dr Michaels® (Fungatinex®) product family.

Candidal intertrigo is an infection of the skin caused by Candida albicans that typically occurs in opposing cutaneous or muco-cutaneous surfaces. Because Candidiasis requires a damaged and moist environment for infection, it typically occurs in areas of friction such as the skin folds of the body. Candidal intertrigo is often difficult to treat and results are often unsatisfactory. In addition, there is a lack of evidence-based literature supporting prevention and treatments for candidal intertrigo. The aim of the study was to evaluate the efficacy of Dr Michaels® (also branded as Fungatinex®) products in the treatment of fungal intertrigo, in 20 women and 2 men with a mean age of 72. Five patients (3 female and 2 male) had type 2 diabetes and 16 (14 female and 2 male) were obese. The patients were treated with Dr Michaels® (Fungatinex®) moisturising bar, topical ointment (twice daily application) and oral herbal formulation, PSC 200 two tablets twice daily with food. After 2 weeks of treatment, the lesions had mostly resolved in all patients with only slight erythema evident. After six weeks of treatment using the moisturising bar, topical ointment and oral herbal formulations from the Dr Michaels® (Fungatinex®) product family, the lesions had totally resolved in 18 patients, while 4 patients had to continue the therapeutic protocol for another 2 weeks. Our results demonstrate that the Dr Michaels® (Fungatinex®) complementary product family is efficacious in the treatment of recalcitrant candidal intertrigo. Furthermore, this study highlights that the Dr Michaels® (Fungatinex®) product family is fast-acting and well tolerated with no serious adverse events reported. These data have important implications for resistant cases of candidal intertrigo where traditional therapies have failed.

Regulatory categories of probiotics across the globe: a review representing existing and recommended categorization.

Probiotics are friendly live microorganisms (in most cases, bacteria) that are similar to beneficial micro-organisms found in the human gut, whenever consumed, have potential to confer benefit to the health of consumers by maintaining, or improving their intestinal microbial flora and are available to consumers mainly in the form of dietary supplements and foods. All-time high interest in the field of probiotics is due to emerging probiotic industry. Probiotics are available in foods and dietary supplements, even as pharmaceutical formulations (capsules, tablets and powders) and in some other forms as well, but their claims of health benefits may challenge the traditional border between food and medicine. A number of probiotic products have been already introduced into the international market as food supplements, dietary supplements, natural health products, functional foods and many more other categories; as a result, the position of regulatory system for probiotics within existing categories become vague and quite unclear. Common terminology for probiotic products has become a necessity to achieve adequate regulatory control for discussion of probiotic-related issues among government, producers and consumers. The lack of a consistent terminology across the globe leads to legal uncertainty and confusion instead of being a direct obstacle for development of a mature market. This article will explain differences in regulatory categorizations across the globe; discuss the terms like food and drugs with a close relationship to probiotics, the problems associated with unsatisfactorily approached categorization as well as suggestive consolidations for the new categorization which will demarcate probiotics into categories explaining their nutritive claims, health claims or both.

Umbilical cord blood plasma vitamin A levels in low birth weight (LBW) babies.

BACKGROUND: Role of vitamin A in reducing the mortality in infants more than six months of age is well known. Supplementing newborn infants with vitamin A within 48 hours of birth reduces infant mortality by almost a quarter, with the greatest benefit to those of low birth weight (LBW). Studies that could highlight deficiency states in neonates, particularly LBW babies by objective measurement of vitamin A levels would help in formulating the recommendations to supplement these babies with vitamin A. METHODS: Cord blood plasma vitamin A levels of 154 LBW babies with birth weight in the range of 1505-2455 were analysed for plasma vitamin A (retinol) levels by HPLC method. Samples of 55 babies with normal birth weight were also analysed. LBW babies were divided into two subgroups of preterm LBW and LBW-term small for gestational age (SGA). RESULTS: Of the 154 babies with LBW, 92 were preterm LBW and 52 were LBW-term SGA. Mean cord blood plasma vitamin A levels were significantly lower in the preterm LBW group (n = 92) compared to levels observed in babies with normal birth weight (n = 55) and LBW-term SGA subgroups (n = 62). There was no significant difference in the mean vitamin A values between the normal birth weight babies and LBW-term SGA group. There was significant positive correlation of cord blood vitamin A levels with birth weight in the entire set of (n = 154) LBW babies (r=0.37, P < 0.0001). CONCLUSION: This study revealed significantly lower cord blood vitamin A levels in the preterm LBW babies. The level of vitamin A in LBW babies also correlated with their birth weight. There are enough evidence to support causative association between vitamin A deficiency state and neonatal morbidity. Simple interventions like vitamin A supplementation during a crucial stage of an infant's life may be beneficial in the long run. There is a need to establish norms for vitamin A levels and seriously examine the role of vitamin A supplementation for LBW babies during the immediate postnatal period.

Mint oil (Mentha spicata Linn.) offers behavioral radioprotection: a radiation-induced conditioned taste aversion study.

Mentha spicata Linn. (mint), a herb well known for its gastroprotective properties in the traditional system of medicine has been shown to protect against radiation-induced lethality, and recently its constituents have been found to possess calcium channel antagonizing properties. The present study examined the behavioral radioprotective efficacy of mint oil (obtained from Mentha spicata), particularly in mitigating radiation-induced conditioned taste aversion (CTA), which has been proposed as a behavioral endpoint that is mediated by the toxic effects of gamma radiation on peripheral systems, primarily the gastrointestinal system in the Sprague-Dawley rat model. Intraperitoneal administration of Mentha spicata oil 10% (v/v), 1 h before 2 Gy gamma radiation, was found to render significant radioprotection against CTA (p < 0.05), by blocking the saccharin avoidance response within 5 post-treatment observational days, with the highest saccharin intake being observed on day 5. This finding clearly demonstrates that gastroprotective and calcium channel antagonizing properties of Mentha spicata can be effectively utilized in preventing radiation-induced behavioral changes.

Herbal intake: undiagnosed hypothyroidism leading to postoperative refractory circulatory collapse--a case report.

There is a high probability of missing out on the preoperative diagnosis of hypothyroidism in elderly females, as most of the symptoms are attributed to old age. We report a patient with undiagnosed hypothyroidism, operated for excisional biopsy of carcinoma of tongue, who postoperatively developed septicemia refractory to maximum ionotropic support and antibiotic coverage and succumbed within 40 hours. Her symptoms of constipation, sedentary life style, and joint pains were attributed to old age by the family and thus were not communicated to us in the preoperative assessment. Her long-standing hypothyroidism probably was associated with adrenocortical suppression exaggerated with intermittent and chronic ingestion of herbal powder, which generally contains steroids. We recommend that a more careful preoperative evaluation and history pertaining to hypothyroidism in obese female patients more than 45 years with joint pains should be sought for. Ingestion of herbal powders should alert us as these contain steroids If there is a suspicion of hypothyroidism, then elective surgery should be deferred to rule out the same due to possibility of progression to myxedema coma under stress of anesthesia and surgery. We also recommend that in these cases preoperative blood cortisol level should be evaluated to rule out adrenocortical suppression and direct its management, if present.

Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.

At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.

Zingiber officinale Rosc. modulates gamma radiation-induced conditioned taste aversion.

The aim of the present study was to investigate the neurobehavioral protective efficacy of a hydroalcoholic extract of ginger (Zingiber officinale Rosc.) in mitigating gamma radiation-induced conditioned taste aversion in Sprague-Dawley rats. Administration of Zingiber extract 1 h before 2-Gy gamma irradiation was effective in blocking the saccharin avoidance response for 5 post-treatment observational days, both in a dose- and time-dependent manner, with 200 mg/kg b.w. i.p. being the most effective dose. Highest saccharin intake in all the groups was observed on the fifth post-treatment day. The potential of ginger extract to inhibit lipid peroxidation induced by radiation (2 Gy) and ascorbate-ion stress in brain homogenate and its ability to scavenge highly reactive superoxide anions were evaluated. The 1000-microg/ml and 2000-microg/ml concentration of ginger extract showed the highest efficiency in scavenging free radicals and in inhibiting lipid peroxidation. The lipid peroxidation and superoxide-anion scavenging ability of the extract further supports its radioprotective properties. The results clearly establish the neurobehavioral efficacy of ginger extract and the antioxidant properties appear to be a contributing factor in its overall ability to modulate radiation-induced conditioned taste aversion. Ginger extract has tremendous potential for clinical applications in mitigation of radiation-induced emesis in humans.

The yeast pheromone-responsive G alpha protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus.

The pheromone response of Saccharomyces cerevisiae is mediated by a receptor-coupled heterotrimeric G protein. The beta gamma subunit of the G protein stimulates a PAK/MAP kinase cascade that leads to cellular changes preparatory to mating, while the pheromone-responsive G alpha protein, Gpa1, antagonizes the G beta gamma-induced signal. In its inactive conformation, Gpa1 sequesters G beta gamma and tethers it to the receptor. In its active conformation, Gpa1 stimulates adaptive mechanisms that downregulate the mating signal, but which are independent of alpha-beta gamma binding. To elucidate these potentially novel signaling functions of G alpha in yeast, epistasis analyses were performed using N388D, a hyperadaptive mutant form of Gpa1, and null alleles of various loci that have been implicated in adaptation. The results of these experiments indicate the existence of signaling thresholds that affect the yeast mating reaction. At low pheromone concentration, the Regulator of G Protein Signaling (RGS) homologue and putative guanosine triphosphatase (GTPase) activating protein, Sst2, appears to stimulate sequestration of G beta gamma by Gpa1. Throughout the range of pheromone concentrations sufficient to cause cell cycle arrest, Gpa1 stimulates adaptive mechanisms that are partially dependent on Msg5 and Mpt5. Gpa1-mediated adaptation appears to be independent of Afr1, Akr1, and the carboxy-terminus of the pheromone receptor.

Lipid peroxide levels in chronic renal failure.

To determine presence of oxidant stress in chronic renal failure and to evaluate the efficacy of vitamin E in its amelioration, we studied 34 patients (Group I, age 32.4 +/- 11 years, M:F 3:1) and 10 healthy controls (Group II, age 27.4 +/- 5 years, M:F 4:1). The difference in baseline values of lipid peroxide (nmol/ml) was statistically significant (Group I 4.19 +/- 1.69, Group II 1.87 +/- 1.39, p = 0.004). Values of vitamin E (mg/l) were also significantly lower in Group I as compared to Group II (12.18 +/- 4.27 vs. 19.32 +/- 2.03, p = 0.003). Serum lipid peroxide values decreased significantly after supplementation with 400 mg/day of vitamin E for six weeks in Group I (4.19 +/- 1.69 to 3.21 +/- 1.13, p = 0.053) but not in Group II (1.87 +/- 1.39 to 1.03 +/- 0.87). Levels of vitamin E increased in both the groups (Group I: 12.18 +/- 4.27 to 16.01 +/- 5.13, Group II: 19.32 +/- 2.03 to 23.21 +/- 1.94, p < 0.005). No significant difference was observed in values of serum creatinine and urea before and after intervention.