Epigallocatechin Gallate Mitigates the Methamphetamine-Induced Striatal Dopamine Terminal Toxicity by Preventing Oxidative Stress in the Mouse Brain

Methamphetamine (METH) is a popular psychostimulant due to its long-lasting effects and inexpensive production. METH intoxication is known to increase oxidative stress leading to neuronal damage. Thus, preventing the METH-induced oxidative stress can potentially mitigate neuronal damage. Previously, our laboratory found that epigallocatechin gallate (EGCG), a strong antioxidant found in green tea, can protect against the METH-induced apoptosis and dopamine terminal toxicity in the striatum of mice. In the present study, we evaluated the anti-oxidative properties of EGCG on the METH-induced oxidative stress using CD-1 mice. First, we demonstrated that mice pretreated with EGCG 30 min prior to the METH injection (30 mg/kg, ip) showed protection against the striatal METH-induced reduction of tyrosine hydroxylase without mitigating hyperthermia. In addition, injecting a single high dose of METH caused the reduction of striatal glutathione peroxidase activity at 24 h after the METH injection. Interestingly, pretreatment with EGCG 30 min prior to the METH injection prevented the METH-induced reduction of glutathione peroxidase activity. Moreover, we utilized Western blots to quantify the glutathione peroxidase 4 protein level in the striatum. The results showed that METH decreased striatal glutathione peroxidase 4 protein level, and the reduction was prevented by EGCG pretreatment. Finally, we observed that the METH-induced increase of striatal catalase and copper/zinc superoxide dismutase protein levels were also attenuated by pretreatment with EGCG. Taken together, our data indicate that EGCG is an effective agent that can be used to mitigate the METH-induced striatal toxicity in the mouse brain.     

A role delineation study of hand surgery in the USA: assessing variations in fellowship training and clinical practice

Background

We examined the fellowship experience of hand surgeons in the USA to identify gaps and variations in exposure to essential skills and knowledge during hand fellowship.

Methods

We conducted a web-based survey of the entire American Society for Surgery of the Hand and American Association for Hand Surgery membership. We inquired about the level of exposure received to 170 knowledge topics and procedures during fellowship. We used factor analysis to group the knowledge topics and procedures into 79 scales of related items and calculated mean exposure ratings for each scale. We compared the ratings between graduates of plastic surgery (PS) and orthopedic surgery (OS) Residency Review Committee (RRC)-accredited fellowships.

Results

Our response rate was 21 % (n?=?562). Plastic surgery RRC-accredited fellowship graduates reported inadequate exposure for proficiency in 22 % (17/79) of the knowledge topic and procedure scales whereas graduates of OS RRC-accredited fellowships reported inadequate exposure for proficiency in 10 % (8/79) of the scales. Moreover, 11 and 21 % of graduates from PS RRC-accredited fellowships reported receiving no exposure in distal radius/ulna and forearm conditions, respectively, whereas only 1 and 2 % of graduates from OS RRC-accredited fellowships reported receiving no exposure in the same domains, respectively.

Conclusions

Hand surgeons reported significant variations in exposure to essential skills and knowledge. Additionally, in a considerable number of knowledge topics and procedures, a majority of participants in both groups reported what they perceived as inadequate or no exposure during their hand surgery fellowship.     

Postoperative complications in bariatric surgery using age and BMI stratification: a study using ACS-NSQIP data

Background

Bariatric surgery results in long-term weight loss and significant morbidity reduction. Morbidity and mortality following bariatric surgery remain low and acceptable. This study looks to define the trend of morbidity and mortality as it relates to increasing age and body mass index (BMI) in patients undergoing bariatric surgery.

Methods

We queried the ACS/NSQIP 2010–2011 Public Use File for patients who underwent elective laparoscopic adjustable banding (LAGB), sleeve gastrectomy (LSG) and gastric bypass (LGBP). Total morbidity and 30-day mortality were evaluated. Logistic regression models were created to estimate the effect of increasing age and BMI on morbidity for these bariatric procedures.

Results

A total of 20,308 laparoscopic bariatric procedures were reviewed (11617 LGBP, 3069 LSG and 5622 LAGB). Overall mortality and morbidity rates were 0.11 and 3.84 %, respectively. The odds of postoperative complications increased by 2 % with each additional year of age (OR 1.02, 95 % CI 1.02–1.03) and every point increase in BMI (OR 1.02, 95 % CI 1.01–1.03). Multiple logistic regression identified COPD, Diabetes, Hypertension, and Dyspnea as major risk factors for postoperative morbidity. Postoperative complications were three times more likely after LGBP (OR 2.87, 95 % CI 2.31–3.57) and two times more likely after LSG (OR 2.06, 95 % CI 1.57–2.72) when compared to patients undergoing LAGB.

Conclusion

Morbidity and mortality increase on a predictable trend with increasing age and BMI. There is increased risk of morbidity for stapling procedures when compared to gastric banding, but this must be considered in context of surgical efficacy when choosing a bariatric procedure. These data can be used in preoperative counseling and evaluation of surgical candidacy of bariatric surgical patients.     

Pharmacokinetics of diminazene in sheep

The pharmacokinetic behavior of diminazene in plasma after administration of 2 mg/kg i.v. and 3.5 mg/kg i.m. was studied in four healthy Dala x Ryggja rams. Following i.v. injection, the data were satisfactorily described by a tri-exponential equation; the apparent volume of distribution at the steady-state was 0.56 +/- 0.04 L/Kg (mean +/- SD; n = 4); total body clearance averaged 1.1 +/- 0.09 ml/kg/min and elimination half-life was 9.30 +/- 1.40 hr. After intramuscular administration peak plasma levels of 6.30-7.57 micrograms/ml were reached in 20 to 45 min and the mean absorption time averaged 5.83 +/- 1.61 hr. Systemic availability relative to the intravenous dose was 95.10 +/- 23.21% and mean residence time averaged 14.16 +/- 1.55 hr. The partition of diminazene between erythrocytes and plasma averaged 0.64 +/- 0.10; plasma protein binding was high (65-85%) and concentration-dependent. Based on the experimental data obtained, an initial i.m. dose of 2.5 mg/kg followed by 2 mg/kg 24 hr later should be safe and effective in cases of babesiosis and trypanosomiasis sensitive to diminazene. A preslaughter withdrawal period of 14-26 days was estimated.     

Is transmyocardial revascularisation of benefit in addition to coronary artery bypass grafting for patients with diffuse coronary disease?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of transmyocardial revascularisation (TMR) in addition to coronary artery bypass grafting (CABG) is of benefit in patients with ischaemic heart disease with areas of ungraftable myocardium. Altogether 233 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that while the society of thoracic surgeons now recommend TMR+CABG, and the available studies indicate that mortality is not increased by this additional procedure, it is currently not clear whether TMR reduces symptoms of angina in addition to CABG alone.     

BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.     

Acute toxicity of crude extracts of Aspergillus quadrilineatus isolated from acha (Digitaria exilis Stapf)

In a survey of fungi and mycotoxin conterminating acha (Digitaria exilis Stapf) in Plateau State of Nigeria, 96 fungal isolates were made. Screening of the fungi isolates for their mycotoxin-producing potentials showed that Aspergillus quadrilineatus (Thom and Raper) produced some of the most toxic mycotoxins. Two extracts of the Aspergillus quadrilineatus (the petroleum ether soluble extracts [PER] and the petroleum ether defatted crude extract [PEDCR]) were tested for acute toxicity in mice, chicks and cattle. The ip LD50 of PER in mice was 1148 mg/kg, and the oral LD50 of PEDCR was 566 mg/kg in mice and 556 mg/kg in chicks. The ip LD50 of PEDCR in mice was 21 mg/kg. The toxic signs of PER and PEDCR in mice and chicks included tachypnea, tachycardia, anorexia, somnolence, diarrhea, coma and death. The main postmortem findings were congestion of heart, liver, kidney and lungs and sloughing of the wall of stomach and hemorrhagic enteritis. The histopathologic findings in dead animals included edema and mild degeneration of the myocardium and necrosis of kidney tubular epithelial cells, hepatocytes and bronchioles. The only clinical observation in 1 calf orally dosed with a culture of Aspergillus quadrilineatus of maize was transient whole body tremors which occurred 1 h after dosing, tachycardia and profuse salivation. No significant histopathologic changes were found in the organs of the sacrificed calf.     

An inulin-type fructan enhances calcium absorption primarily via an effect on colonic absorption in humans

Calcium absorption efficiency and bone mineral mass are increased in adolescents who regularly consume inulin-type fructans (ITF). The mechanism of action in increasing absorption is unknown but may be related to increased colonic calcium absorption. We conducted a study in young adults designed to evaluate these mechanisms with a kinetic technique using (42)Ca orally and (46)Ca dosed i.v. Those who responded to 8 wk of supplementation with 8 g of a mixed short and long degree of polymerization ITF by increasing their calcium absorption had kinetic measurements analyzed to evaluate the time course of absorption. The area under the curve of the oral tracer in the blood during the 26 h after dosing was calculated and the time dependence of increased absorption determined. Eight young adults (of 13 studied), with mean calcium intake approximately 900 mg/d, responded to the ITF with an increased calcium absorption of at least 3%. In responders, absorption increased from 22.7 +/- 11.3% to 31.0 +/- 15.3%. Colonic absorption, defined as absorption that occurred >7 h after oral dosing, represented 69.6 +/- 18.6% of the increase, or 49 +/- 28 mg/d. These findings suggest that, in those who respond to ITF, its effects on calcium absorption occur principally in the colon. This benefit to ITF may be especially important when absorption in the small intestine is impaired for anatomic or physiological reasons.     

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.