Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18- to 87-Year-Old Men.

OBJECTIVES: Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown. METHODS: We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed. RESULTS: We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m2, 7.65 ± 0.92 kg/m2, 6.87 ± 0.93 kg/m2, for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men. CONCLUSION: Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.

Biomarkers of Physical and Mental Health for Prediction of Parkinson's Disease: A Population-Based Study from 15 European Countries.

OBJECTIVES: Early diagnosis of Parkinson's disease (PD) is critical for optimal treatment. However, the predictive potential of physical and mental health in PD is poorly characterized. METHODS: We evaluated the potential of multiple demographic, physical, and mental factors in predicting the future onset of PD in older adults aged 50 years or older from 15 European countries. Individual study participants were followed over four waves of the Survey of Health, Ageing, and Retirement in Europe (SHARE) from 2013-2020. RESULTS: Of 57,980 study participants, 442 developed PD during the study period. We identified male sex and advancing age from the sixth decade of life onward as significant predictors of future PD. Among physical factors, a low handgrip strength (HGS; men <27 kg, women <16 kg), being bothered by frailty, and recent falls were significantly associated with future PD. Among mental factors, a higher depression (Euro-D depression score >6) emerged as an independent predictor of future PD. Finally, the presence of hypertension or Alzheimer's disease (AD) increases the risk of future PD. CONCLUSIONS: Altogether, male sex, advancing age, low HGS, frailty, depression, hypertension, and AD were identified as critical risk factors for future PD. Our results may be useful in the early identification and treatment of populations at risk for PD.

Time-related changes in the knowledge of HIV/AIDS among followers of various religions in India.

Background: The public knowledge levels about Human Immunodeficiency-Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) have been assessed in previous studies; however, time-related trends in association with socio-demographic standards among the followers of major religions in India are not known. Objectives: We assessed the 2005-06, 2015-16, and 2019-21 demographic and health survey (DHS) data from India to investigate trends in the levels of knowledge of HIV/AIDS among Hindus, Muslims, and Christians in relation to standard socio-demographic variables over a period of 16 years. Methods: The age range of the population was 15-54 years (n=611,821). The HIV/AIDS-related knowledge was assessed by developing a composite index based on ten questions about several aspects of HIV/AIDS, such as the mode of spread. We applied Chi-square and Kruskal-Wallis tests to investigate whether people had heard about HIV/AIDS and their overall HIV knowledge in relation to several socio-demographic standards. Results: Generally, a higher increase in knowledge level was found between the first and second DHS surveys (2006-2016) as compared to between the second and third DHS surveys (2016-2021). We found the highest increase in the level of HIV/AIDS knowledge among Christian women followed by Hindus, whereas Muslims had the least increase over 16 years. Being a female, uneducated, poor, previously married, or having rural residence were associated with the highest increase in the knowledge of HIV/AIDS. Conclusion: Christian women had the highest increase in HIV/AIDS-related knowledge then came Christian men and followers of other religions. We also found the highest increase in HIV/AIDS-related knowledge among the poorest, uneducated, and rural residents. Our findings may help formulate public health strategies targeting various less knowledgeable groups to reduce the incidence of HIV/AIDS.

The quality of life in Alzheimer's disease is not associated with handgrip strength but with activities of daily living-a composite study from 28 European countries.

OBJECTIVES: The relationship between handgrip strength (HGS) and quality of life is inconsistent. The purpose of this study was to investigate the potential association between HGS and quality of life in the settings of ageing and Alzheimer's disease (AD). METHODS: We investigated the HGS, CASP-12 (control, autonomy, self-realization, and pleasure) measure of quality of life, and physical capacity in European adults above 50, including controls (n = 38,628) and AD subjects (n = 460) using the survey of health, ageing, and retirement in Europe (SHARE; 2022). RESULTS: AD subjects exhibited lower HGS and CASP-12 scores than controls (both p < 0.05). Participants with higher CASP-12 quartiles had higher HGS in controls but not in AD subjects. A linear positive relation was found between HGS and CASP-12 in controls (0.0842, p < 0.05) but not in AD subjects (0.0636, p = 0.091). There was no effect of gender on this finding. Lastly, we found significant negative associations of difficulties walking, rising from chair, climbing stairs, and fatigue with CASP-12 scores in controls and AD subjects (all p < 0.05). CONCLUSIONS: Altogether, HGS was not associated with quality of life in individuals with AD. Conversely, difficulties in activities of daily living seem to be negatively associated with quality of life; thus, strategies are recommended to improve physical capacity.

Circulating follicle stimulating hormone levels influence body growth in pre-menarcheal girls in a latitude-dependent manner.

Introduction: Age at menarche is an essential determinant of reproductive life of a woman. Latitude is an important driver of age at menarche, however the contributions of circulating follicle stimulating hormone (FSH) and socio-economic status (SES) to age at menarche in a latitude-dependent manner is not known. Methods: This population-based cross-sectional study is a component of our major cohort of 10,050 schoolgirls aged 8-16 years from 35 schools across 10 districts. The selected districts were categorised into high and low latitudes by applying a cut-off point at latitude 31.5°N. We evaluated the physical parameters, SES, circulating FSH, and growth hormone (GH) levels in pre-menarche girls (N = 252) at different latitudes. Results: Self-reported age at menarche of girls residing at different latitudes in Pakistan showed that higher latitude is associated with delayed age at menarche. Higher latitude was associated with reduced circulating FSH levels, as well as lower parameters of physical growth including body mass index (BMI), waist-hip ratio and, waist-height ratio (all p < 0.05) in the pre-menarcheal girls. However, circulating GH levels were not affected by latitude. On the other hand, lower SES was associated with reduced GH levels and lower BMI, which are considered as probably the primary determinants of physical growth. Conclusions: Taken together, we show that higher latitude may delay the sexual maturation, while poor SES may delay the physical growth in girls.

One Year of Experience Managing Peritonitis Secondary to Gastrointestinal Perforation at a Tertiary Care Hospital: A Retrospective Analysis.

Introduction Peritonitis secondary to gastrointestinal perforation causes high morbidity and mortality rates in the emergency department with an immediate need for surgical intervention. Despite improved surgical management procedures, patients are still suffering from gastrointestinal leak causing peritonitis that demands surgical management by highly skilled surgeons in high-quality surgical units. Material and methods This paper presents one year of experience in the surgical treatment of gastrointestinal perforation-related peritonitis by surgeons in Lahore General Hospital, Lahore, Pakistan. Data was retrospectively collected from patient records and quantitatively analyzed. Involved patients developed peritonitis secondary to gastrointestinal perforation requiring surgical exploration and interventions in the emergency department between November 2020 and October 2021. Results One hundred and fifty-eight patients were involved; the mean age was 43.46 years. The number of males was 87 (55.06%). The patients mostly presented with generalized abdominal pain (57.6%). All the patients had perforation-related peritonitis, which was most prevalent in the ileum (62%). The most performed surgical intervention was loop ileostomy (36.71%). Compared to other published reports, the incidence rate of wound dehiscence in the hospital was relatively higher. Postoperatively, wound infection was low if the skin was left open (23.62%) compared to closed skin (38.7%). Patient outcomes were acceptable as the death rate was low (3.2%, 5/158). Conclusion Peritonitis caused by gastrointestinal perforation is associated with a high risk of morbidity that necessitates surgical exploration. Leaving skin wound open after the surgical intervention is recommended to decrease the incidence of wound infection and dehiscence.

Growth and socio-economic status, influence on the age at menarche in school going girls.

INTRODUCTION: Onset age at menarche has been considered an important indicator of reproductive maturity in females and reflects the health status of the population. The purpose of this study was to determine the mean menarcheal age and to examine whether anthropometric and socio-economic status (SES) influences age at menarche in the girls from Punjab province of Pakistan. METHODS: In this population-based cross-sectional study, 10,050 school-going girls aged 8-16 years from 35 schools across 12 districts of Punjab were recruited. Menarcheal data was obtained by using a questionnaire, while the anthropometric data were obtained by the measurements of standing height, body weight, waist, and hip circumference. The anthropometric indices of pre- and post-menarcheal girls were compared. Student's t-test, ANOVA, and post-hoc Tukey's test was applied for comparison between two and multiple groups respectively, P < 0.05 was considered statistically significant. RESULTS: There was a normal distribution of age at menarche and mean was 12.4 years in the study population. The girls who reached menarche were found to be taller and heavier with higher BMIs, having a greater waist and hip circumference as compared to their pre-menarcheal peers. Waist-hip-ratio was less, and the waist-to-height ratio was higher in post-menarcheal as compared to pre-menarcheal girls. The girls belonging to low SES had delayed onset of menarche as compared to those belonging to middle/high SES. CONCLUSION: The age at menarche was associated with SES and changes in various anthropometric measurements reflecting the growth status of girls.

Atomoxetine for amphetamine-type stimulant dependence during buprenorphine treatment: A randomized controlled trial.

BACKGROUND: Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder. METHODS: Participants with opioid and ATS dependence (N = 69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80 mg daily (n = 33) or placebo (n = 33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen's d for the intention-to-treat (ITT) sample and for higher adherence subsample (≥60 days of atomoxetine or placebo ingestion). RESULTS: Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67 (0.53-0.81, d = 0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78, d = 0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p < 0.001) and did not differ significantly between atomoxetine- and placebo-treated participants (p = 0.42). Depressive symptoms were reduced from baseline in both groups (p < 0.02) with a greater reduction for atomoxetine- than placebo-treated participants (p < 0.02). There were no serious adverse events or adverse events leading to medication discontinuation. CONCLUSIONS: The findings support clinical tolerability and safety and suggest potential efficacy of atomoxetine for treating ATS use disorder in this population.

Effects of food price shocks on child malnutrition: The Mozambican experience 2008/2009.

A propitiously timed household survey carried out in Mozambique over the period 2008/2009 permits us to study the relationship between shifts in food prices and child nutrition status in a low income setting. We focus on weight-for-height and weight-for-age in different survey quarters characterized by very different food price inflation rates. Using propensity score matching techniques, we find that these nutrition measures, which are sensitive in the short run, improve significantly in the fourth quarter of the survey, when the inflation rate for basic food products is low, compared to the first semester or three quarters, when food price inflation was generally high. The prevalence of underweight, in particular, falls by about 40 percent. We conclude that the best available evidence points to food penury, driven by the food and fuel price crisis combined with a short agricultural production year, as substantially increasing malnutrition amongst under-five children in Mozambique.

Antibiotic stewardship: a focus on ambulatory care.

Antibiotic resistance is one of the major health threats facing modern medicine. While there are many tactics to address this issue, antibiotic stewardship has been shown effective in reducing antimicrobial resistance, adverse drug effects, mortality and health care cost. Most antibiotic stewardship programs have evolved within acute care settings where the bulk of resistant infections are identified. Unfortunately, hospitals are just the tip of the iceberg in terms of overall antibiotic use. The vast majority of the antibiotic prescriptions are dispensed in ambulatory care settings, making this a critical target for stewardship programs. This article discusses the global need for antibiotic stewardship, highlights the importance of outpatient stewardship, and discusses strategies and challenges for implementation of stewardship in community settings.

Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction of Terminalia chebula.

Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500 mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60 min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10 mg/kg; i.p., dextromethorphan 10 mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265 mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3 mg/kg; s.c.) while rimcazole (3 mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated.

Orosomucoid serum concentrations and fat depot-specific mRNA and protein expression in humans.

Obesity is associated with chronic low-grade inflammation, which contributes to systemic metabolic irregularities and obesity-linked metabolic disorders. Orosomucoid (ORM), an acute phase reactant protein, was shown to be produced in response to metabolic and inflammatory signals in the adipose tissue of obese mice, which protects them from severe inflammation and subsequent metabolic dysfunction. In this study, we examined whether there are site-specific differences between visceral and subcutaneous adipose tissue (VAT and SAT, respectively) ORM gene and protein expression from individuals with a wide range of obesity and the relationship between expressed and circulating ORM levels and measures of adiposity, insulin resistance, and pro- and anti-inflammatory markers and adipokines. The level of circulating ORM correlated positively with BMI, body fat mass, and serum leptin. It also correlated with fasting insulin, HOMA-IR values and C-reactive protein in men. There were no site-specific differences in ORM mRNA and protein expression between VAT and SAT, nor did we find a relationship between circulating ORM levels and its mRNA expression in either fat depot. We found that ORM mRNA expression correlated with mRNA expression of TNF-α, IL-6, and adiponectin in VAT, and with TNF-α and adiponectin in SAT. These observations are the first description linking adipose tissue ORM and pro- and anti-inflammatory molecules in humans. The close links of ORM and measures of adiposity, insulin resistance, and adipose tissue inflammation in humans reinforce previous experimental data and warrant further studies to explore a possible role of ORM in the pathogenesis of obesity-associated metabolic derangements.

Effect of carvedilol on portal pressure estimated by hepatic vein Doppler ultrasound waveform and damping index in cirrhotic patients.

OBJECTIVE: To assess the effect of Carvedilol in reducing portal pressure estimated non-invasively by studying Doppler ultrasound waveforms (DUS) and hepatic vein Damping Index (DI). STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: Department of Medical ICU in collaboration with Department of Radiology, JPMC, over a period of 6 months (June 1st to 30th November, 2008). METHODOLOGY: Of the enrolled 65 patients, 47 patients (33 males and 14 females) completed the study. The mean age was 47.4 years. Cirrhotic patients of Hepatitis B, C, D (delta), B and C combined, B and D combined with varying degrees of portal hypertension were included in the study. Cirrhotic patients with bronchial asthma, congestive heart failure, Insulin dependent Diabetes, portal vein thrombosis and hepatorenal syndrome were excluded from the study. The patients were examined by color flow Doppler of the right hepatic vein before and after administration of Carvedilol. Their waveforms and Damping Index (DI) were recorded and compared by Wilcoxon signed ranks test through SPSS version 12.0. Responders were described as those showing a positive change in wave forms or a decrese of 0.10 or more in DI. RESULTS: Of the 47 patients, 30 (63%) showed a positive response and 10 (21%) showed no favorable response to Carvedilol, while 7 (14%) patients showed deterioration. The mean DI on DUS dropped from 0.62 to 0.41 in responders after treatment, while in the non-responders it ranged between 0.42 and 0.57. CONCLUSION: Ultrasonography Carvedilol reduced portal pressure of cirrhotic patients, as measured indirectly by the damping index of hepatic waveform by Doppler.

Seat belt trauma: pectoralis muscle rupture and delayed mesh repair.

To our knowledge, this is the first reported case of a seat belt-related rupture of the pectoralis major muscle and its successful delayed repair using mesh. We report a case of a 34-year-old white man who sustained a right pectoralis major muscle rupture from a seat belt during a motor vehicle crash. The patient presented to us 2 years after the injury. We introduce a technique using mesh that results in a successful repair of a cosmetically disfiguring chest wall defect.

Hemodynamic effects of terlipressin in patients with bleeding esophageal varices secondary to cirrhosis of liver.

OBJECTIVE: To study the hemodynamics of terlipressin in bleeding esophageal varices due to cirrhosis of the liver. DESIGN: A quasi-experimental study. PLACE AND DURATION OF STUDY: Medical-ICU, Jinnah Postgraduate Medical Centre, Karachi from February to July 2005. PATIENTS AND METHODS: Seventy-eight consecutive patients with bleeding esophageal varices were evaluated. The diagnosis of cirrhosis was based on history, physical examination, laboratory data and abdominal ultrasound. Blood-pressure and pulse rate were monitored. Injection terlipressin 2 mg intravenous bolus was given followed by 2 mg i/v 6 hourly. Intravenous plasma expanders, whole blood, fresh frozen plasma and platelet concentrates were transfused as needed. Upper gastrointestinal endoscopy was performed for evaluation and grading of varices, detection of portal gastropathy, and banding. Descriptive and inferential statistics were applied as applicable. RESULTS: Seventy patients of either gender, aged 18 - 95 years were included in the study. Systolic blood-pressure(SP) increased by 7.77 mmHg (mean SP: 108.1 mmHg, SD + 9.84, 95% CI: 105.77 - 110.43 mmHg; p-value: 0.0002); diastolic blood-pressure(DP) by 21.57 mmHg (mean DP: 79.71 mmHg, SD + 7.35, 95% CI: 77.97 - 81.45 mmHg; p-value: 0.001) and mean arterial pressure by 9.42 mmHg(mean MAP: 89.12 mmHg, SD + 6.98, 95% CI: 87.45 - 90.78 mmHg; p-value: 0.0007) within 24 hours of initiating terlipressin in majority of patients. The pulse rate decreased in 34 (48.5%) patients by 6-24 beats/min in 30 min, and by 2-12 beats/min in 24 hours; and increased in 30 (42.85)% patients by 10-15 beats/min at 30 min and by 2-8 beats/min at 24 hours. CONCLUSION: Terlipressin had an overall benefit in significant number of patients with bleeding esophageal varices in this series and only a few adverse effects when given at recommended doses.

Cortical neuronal and glial pathology in TgTauP301L transgenic mice: neuronal degeneration, memory disturbance, and phenotypic variation.

Recapitulation of tau pathologies in an animal model has been a long-standing goal in neurodegenerative disease research. We generated transgenic (TgTauP301L) mice expressing a frontotemporal dementia with parkinsonism linked to chromosome 17 (FTPD-17) mutation within the longest form of tau (2N, 4R). TgTauP301L mice developed florid pathology including neuronal pretangles, numerous Gallyas-Braak-positive neurofibrillary tangles, and glial fibrillary tangles in the frontotemporal areas of the cerebrum, in the brainstem, and to a lesser extent in the spinal cord. These features were accompanied by gliosis, neuronal loss, and cerebral atrophy. Accumulated tau was hyperphosphorylated, conformationally changed, ubiquitinated, and sarkosyl-insoluble, with electron microscopy demonstrating wavy filaments. Aged TgTauP301L mice exhibited impairment in hippocampally dependent and independent behavioral paradigms, with impairments closely related to the presence of tau pathologies and levels of insoluble tau protein. We conclude that TgTauP301L mice recreate the substantial phenotypic variation and spectrum of pathologies seen in FTDP-17 patients. Identification of genetic and/or environmental factors modifying the tau phenotype in these mice may shed light on factors modulating human tauopathies. These transgenic mice may aid therapeutic development for FTDP-17 and other diseases featuring accumulations of four-repeat tau, such as Alzheimer's disease, corticobasal degeneration, and progressive supranuclear palsy.

Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases.

Gamma-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex. This endoproteolytic activity cleaves within transmembrane domains of amyloid-beta precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-beta (Abeta) 40 peptide to greater production of Abeta42. Although studies in PS1/PS2-deficient embryonic cells define overlapping activities for these proteins, in vivo complementation of PS1-deficient animals described here reveals an unexpected spectrum of activities dictated by PS1 and PS2 alleles. Unlike PS1 transgenes, wild-type PS2 transgenes expressed in the mouse CNS support little Abeta40 or Abeta42 production, and FAD PS2 alleles support robust production of only Abeta42. Although wild-type PS2 transgenes failed to rescue Notch-associated skeletal defects in PS1 hypomorphs, a "gained" competence in this regard was apparent for FAD alleles of PS2. The range of discrete and divergent processing activities in mice reconstituted with different PS genes and alleles argues against gamma-secretase being a single enzyme with intrinsically relaxed substrate and cleavage site specificities. Instead, our studies define functionally distinct gamma-secretase variants. We speculate that extrinsic components, in combination with core complexes, may tailor functional variants of this enzyme to their preferred substrates.

Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice.

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).

Effect of Rheum emodi (Revand Hindi) on renal functions in rats.

The renal effects of water-soluble (W-S) and water-insoluble (W-INS) portions of the alcoholic extract of Revand Hindi (Rheum emodi) were investigated on cadmium chloride, mercuric chloride, potassium dichromate and gentamicin-induced nephrotoxicity in rats and normal rats by monitoring the levels of urea nitrogen and creatinine in serum. The present investigations provide evidences that W-S fraction has nephroprotective effect on all the proximal tubule segments (S1, S2 and S3) possibly through antioxidant action of the tannins present in the fraction. W-INS also improved the renal function by protecting S2 segment of proximal tubule nephrotoxicity induced by metals viz cadmium chloride and mercuric chloride in rat models, however, this fraction has been found to enhance gentamicin nephrotoxicity.