Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.     

Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by diallyl trisulfide

The present investigation was aimed to investigate the possible protective role of diallyl trisulfide (DATS) against arsenic (As)-induced hepatic mitochondrial toxicity in rats. Mitochondria were isolated from the liver tissue of rats from all the groups. Lipid profile, lipid peroxidation, antioxidant enzyme activities, hepatic function enzymes, mitochondrial swelling, cytochrome c oxidase activity, mitochondrial Ca⁺-ATPase and Na⁺/K⁺-ATPase activity, mitochondrial calcium content and mitochondrial enzyme activities were measured. Short-term As exposure (5?mg/kg?bw/d for 28?d) caused liver damage as evidenced by changes in activities of liver enzymes. The effects of As were coupled with enhanced reactive oxygen species generation, mitochondrial swelling, inhibition of cytochrome c oxidase, complex I-mediated electron transfer, decreased Ca²⁺-ATPase and Na⁺/K⁺-ATPase activity, a reduction in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress, significant increase in mitochondrial lipid peroxidation products and alterations in mitochondrial lipid profile. Significant decreases in mitochondrial antioxidants and tricarboxylic acid cycle enzymes were also found in the liver mitochondria of As-induced hepatic mitochondrial toxicity in rats. As also increased hepatic caspase-3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by As could be alleviated by supplementation with DATS, which likely suggests a protective role against As-induced hepatotoxic changes and hepatic mitochondrial toxicity. The protective effect of DATS on the liver mitochondria was evidenced by altering all the changes induced by As. Free radical scavenging and metal chelating activities of DATS may be the mechanism, responsible for the protective action against As-induced mitochondrial damage in liver.     

Profile of women substance users seeking treatment at tertiary care treatment center in India: A retrospective chart review study

Introduction: Among substance users, women represent a small, unique subpopulation. Studying their socio-demographic and substance-use profile helps us understand their concerns and formulate management strategies. Materials and Methods: In this retrospective chart review, all the available records of outpatient treatment seekers at National Drug Dependence Treatment Centre (NDDTC), All India Institute of Medical Sciences (AIIMS), Ghaziabad, from 1 January 2011 to 31 December 2015 were screened. Data from the women substance users were entered into a specially designed MS Excel format and analyzed. Results: In these 5 years, 217 women (mean age 36.75 ± 11.84 years) sought treatment. Majority were married (75.6%), housewife (53.5%), educated (59.4%), from an urban background (70.0%). Most common primary substance used was opioid (61.3%), including heroin (30.0%) and pentazocine (16.1%). About 20.3% reported injectable opioid use. The mean duration of opioid use was 5.44 ± 4.68 years. History of prior treatment seeking was reported by 4.6% and no prior significant abstinence attempts by 77.4%. Discussion and Conclusion: Majority of female treatment seekers, are young, married urban women and seek treatment for opioid use, particularly heroin (as opposed to pentazocine, suggested by previous studies). Prior treatment seeking and abstinence rates are low. Data indicates the need of specialized services for this population.     

High proportion of pentazocine dependence among treatment-seeking female injecting drug users (FIDUs) in India: A distinct population?

Background. Adverse consequences of injecting are greater among female injecting drug users (FIDUs), yet treatment-seeking is low because of stigma, poor social support, and unavailability of gender-specific services. FIDUs, despite being a distinct subpopulation of women substance users, are sparsely studied.

Aims. We aimed to study the sociodemographic and clinical profile of treatment-seeking FIDUs at a tertiary drug treatment center in North India.

Methods. In this retrospective study, we reviewed medical records of all the FIDUs who sought outpatient treatment from January 1, 2011, to December 31, 2015.

Results. Out of a total of 217 records of female patients, 44 were current IDUs (20.27%), with mean age 35.48 ± 10.13 years. Majority were Hindu (84.1%), married (81.8%), homemakers (52.3%) educated up to 12 years (65.9%). Primary drug of dependence was injection pentazocine for 33 patients (75.0%) and injection smack (street heroin) for 8 (18.2%). Commonest reason for initiation of drug use was iatrogenic (n = 25; 56.8%). Major physical complications were reported by 29 (65.9%), while 12 (22.8%) reported psychiatric comorbidity.

Conclusion. A typical treatment-seeking FIDU is middle-aged, educated, homemaker using injecting pentazocine. High rate of injecting with iatrogenic onset highlights the need for women-specific services as well as awareness-building among physicians.     

Physical and Biochemical Characterization of Chemically Treated Pollen Shells for Potential Use in Oral Delivery of Therapeutics

Allergen-free pollen shells obtained from natural pollen grains have recently attracted attention as microcapsules for oral therapeutic delivery. We have recently developed a chemical treatment method that enables successful retrieval of hollow pollen shells from diverse species. A comprehensive characterization is critical to characterize the effects of chemical treatment which will not only benchmark the pollen treatment process but can also lay the foundation of quality control procedures to check allergen-removal efficiency during pollen treatment. Therefore, in this study, we followed the effects of chemical treatment on 4 different pollen species using electron microscopy, elemental analysis, gel electrophoresis, confocal microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. These analyses revealed that acetone treatment removed lipids from the pollen surface. Phosphoric acid treatment removed proteins and nucleic acids from the pollen core and transformed esters into carboxylic acids. Potassium hydroxide hydrolysis changed carbohydrate composition of the pollen wall. Chemically treated pollen shells exhibited hydroxyl and carboxyl functional groups on their surface. Overall, we propose that confocal microscopy could be used as a rapid scanning technique to visualize the removal of biomolecules, whereas Fourier-transform infrared combined with gel electrophoresis could be used as a more objective approach for analysis and benchmarking.     

Variation in quality of care among older men with localized prostate cancer

BACKGROUND:

The objective of this study was to assess the racial and ethnic disparities in outcomes and their association with process‐of‐care measures for elderly Medicare recipients with localized prostate cancer.

METHODS:

The Surveillance, Epidemiology, and End Results‐Medicare databases for the period from 1995 to 2003 were used to identify African‐American men, non‐Hispanic white men, and Hispanic men with localized prostate cancer, and data were obtained for the 1‐year period before the diagnosis of prostate cancer and up to 8 years postdiagnosis. The short‐term outcomes of interest were complications, emergency room visits, readmissions, and mortality; the long‐term outcomes of interest were prostate cancer‐specific mortality and all‐cause mortality; and process‐of‐care measures of interest were treatment and time to treatment. Cox proportional hazards regression, logistic regression, and Poisson regression were used to study the racial and ethnic disparities in outcomes and their association with process‐of‐care measures.

RESULTS:

Compared with non‐Hispanic white patients, African‐American patients (Hazard ration [HR], 1.43; 95% confidence interval [CE], 1.19‐1.86) and Hispanic patients (HR=1.39; 95% CI, 1.03‐1.84) had greater hazard of long term prostate specific mortality. African‐American patients also had greater odds of emergency room visits (odds ratio, 1.4; 95% CI, 1.2‐1.7) and greater all‐cause mortality (HR, 1.39; 95% CI, 1.3‐1.5) compared with white patients. The time to treatment was longer for African‐American patients and was indicative of a greater hazard of all‐cause, long‐term mortality. Hispanic patients who underwent surgery or received radiation had a greater hazard of long‐term prostate‐specific mortality compared with white patients who received hormone therapy.

CONCLUSIONS:

Racial and ethnic disparities in outcomes were associated with process‐of‐care measures (the type and time to treatment). The current results indicated that there is an opportunity to reduce these disparities by addressing these process‐of‐care measures. Cancer 2011. © 2010 American Cancer Society.     

Perforated tubercular enteritis of childhood: A ten year study

One hundred sixty seven children were operated at the Kalawati Saran Children Hospital for acute peritonitis during last 10 years (1978–88). Bowel perforation was seen in 123 cases. Nineteen cases had underlying Tubercular enteritis. Preoperative diagnosis was usually difficult. The terminal ileum was affected in 12 and the jejunum in 5 cases. Multiple perforations were seen in 3 cases. Postoperative mortality was high (12/19) and usually attributable to their poor preoperative status.     

Acanthosis nigricans in a plaque of scleredema on the back of a diabetic patient: a case report

Acanthosis nigricans (AN) and scleredema are two skin conditions that have been reported in association with diabetes mellitus. Few cases associating scleredema and AN have been reported. A literature search did not reveal any reports of diabetic patients developing AN on top of a scleredema plaque. Here we report a patient with diabetes mellitus who developed AN within the same indurated scleredema plaque.     

Effect of acupuncture on knee function in advanced osteoarthritis of the knee: a prospective, non-randomised controlled study

We report a prospective controlled trial, comparing acupuncture with no treatment, in patients with advanced osteoarthritis of the knee awaiting total knee replacement. Knee function was assessed at the beginning of study and at the end of two months, using four parameters: HSS score, time to walk 50 metres, time to climb 20 steps, and degree of pain. Acupuncture was given at four local points around the knee and at one distal point. The acupuncture group improved in all parameters, whereas the control group deteriorated, a finding that was highly statistically significant (p < 0.0002). Further randomised-controlled trials with longer follow-up are required to confirm these findings.