Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.     

Direct observation therapy with appropriate treatment regimens was associated with a decline in second-line drug-resistant tuberculosis in Taiwan

The resistance of Mycobacterium tuberculosis (MTB) to second-line drugs (SLDs) is growing worldwide; however, associations between the appropriateness of treatment for tuberculosis (TB) and whether the directly observed treatment, short course (DOTS)/DOTS-plus programs had an impact on the prevalence of SLD-resistant MTB are still uncertain. We performed a retrospective analysis of resistance profiles among MTB isolates obtained from 6,035 consecutive patients from 2004 to 2011 at two TB referral hospitals in Taiwan. There was a significant decrease (all p-values <0.01) in the prevalence of MTB isolates that were resistant to fluoroquinolones, injectable SLDs, and orally administered SLDs, and multidrug-resistant (MDR) and extensively drug-resistant (XDR) MTB isolates over time. There was a significant increase in the coverage rate of DOTS/DOTS-plus programs and that of administering appropriate first-line and second-line regimens (all p?<?0.01). Compared with isoniazid-susceptible isolates, high-level (1.0 mg/L) isoniazid-resistant and MDR isolates showed extensive cross resistance to ofloxacin (5.9 %, p?<?0.01 and 33.6 %, p?<?0.01), levofloxacin (9.6 %, p?<?0.01 and 38.1 %, p?<?0.01), moxifloxacin (11.1 %, p?<?0.01 and 26.5 %, p?<?0.01), kanamycin (6.8 %, p?<?0.01 and 16.7 %, p?<?0.01), ethionamide (6.4 %, p?<?0.01 and 16.2 %, p?<?0.01), and para-aminosalicylic acid (13.1 %, p?<?0.01 and 20.4 %, p?<?0.01), but not to capreomycin (2.0 %, p?=?0.06 and 1.6 %, p?=?0.08). The decline in prevalence of resistance to SLDs was negatively correlated with the rise in rates of administering appropriate regimens as well as the DOTS/DOTS-plus programs, but not with the increase in usage of second-line regimens. The implementation of DOTS/DOTS-plus programs with appropriate regimens was associated with a decrease in the prevalence of SLD-resistant and XDR TB.     

Temporal prominence of auditory evoked potentials (N1 wave) in 4-8-year-old children

Cortical auditory evoked potentials (N1 wave) were studied in 24 adults (12 men, 12 women) and 20 children (12 boys, 8 girls; age: 4-8 years). In adults, this wave was recorded with maximal amplitude at frontocentral sites, peaking at about 100 ms poststimulation, whereas in children the auditory response displayed maximal amplitude at the midtemporal sites, with a positive wave at about 100 ms and a large negative wave at approximately 170 ms. Moreover, the modulatory effects of intensity on N1 amplitude were prominent at frontocentral sites in adults and at temporal sites in children. Frontocentral negative response was also recorded in children but was smaller in amplitude and longer in peak latency (around 140 ms) than in adults; responses were of greater amplitude at the frontal site than at the vertex before 6 years of age, whereas the reverse was more often found after this age. These data suggest great differences with age in the neural generators contributing to auditory evoked potentials recorded in the N1 latency range.     

IMMUNOHISTOCHEMICAL DISTRIBUTION OF CANNABINOID CB 1 RECEPTOR IN THE RAT CENTRAL NERVOUS SYSTEM

IMMUNOHISTOCHEMICAL DISTRIBUTION OF CANNABINOID CB 1 RECEPTOR IN THE RAT CENTRAL NERVOUS SYSTEM@邹冈     

Suppression of noxious stimulus-evoked expression of Fos protein-like immunoreactivity in rat spinal cord by a selective cannabinoid agonist

In rats, cannabinoids inhibit behavioral responses to noxious stimulation with a potency and efficacy similar to that of morphine. However, because cannabinoids depress motor function, it has not been possible to state beyond any doubt that these effects were related to a dampening of noxious sensory input. Therefore, c-fos immunocytochemistry was used to explore the possibility that cannabinoids reduce behavioral responses to noxious stimuli by decreasing spinal processing of nociceptive inputs. Rats received systemic injections of the potent and selective cannabinoid agonist WIN 55,212-2, the receptor-inactive enantiomer WIN 55,212-3 or vehicle prior to observations in a model of tonic pain, the formalin test. As demonstrated previously, plantar injections of formalin led to lifting and licking of the injected paw, with two peaks of activity occurring at 5 and 30 min after injection. The cannabinoid agonist suppressed these pain responses and produced a reduction in mobility. Immunocytochemical processing of sections with an antibody to the Fos protein revealed that the cannabinoid markedly suppressed pain-evoked c-fos expression in the superficial and neck regions of the spinal dorsal horn, but not in the nucleus proprius. Decreased expression of c-fos also occurred in the ventral horn. The specificity of this effect and its probable mediation by cannabinoid receptors are suggested by three findings: (i) the suppression by the drug of both behavioral and immunocytochemical responses to pain was dose-dependent; (ii) neither the behavioral nor the immunocytochemical response to the noxious stimulus was significantly affected by the receptor-inactive enantiomer of the agonist; (iii) animals rendered tolerant to cannabinoids by repeated injections of the agonist showed reduced responses to the drug. These findings suggest that cannabinoids inhibit the spinal processing of nociceptive stimuli and support the notion that endogenous cannabinoids may act naturally to modify pain trnasmission within the central nervous system.     

Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S - methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.      

The Correlation Between CVP and SVV and Intraoperative Minimal Blood Loss in Living Donor Hepatectomy

Background

Blood loss during liver surgery is found to be correlated with central venous pressure (CVP). The aim of the current retrospective study is to find out the cutoff value of CVP and stroke volume variation (SVV), which may increase the risk of having intraoperative blood loss of more than 100 mL during living liver donor hepatectomies.

A useful alternative surgical technique to reconstructing large defects following excision of recurrent pilonidal sinus disease in the intergluteal region: An operative approach for the transverse lumbar artery perforator flap

The reconstruction of defects in the intergluteal region following pilonidal sinus excision is challenging due to its anatomical location, close proximity to the anus, and being a high‐tension area prone to wound‐healing problems. Excision and primary closure is known to carry a higher risk of recurrence and subsequent complications compared with using nearby local healthy tissue, such as a flap, to reconstruct defect. Extra due diligence should be given to patient selection and flap choice when deciding the reconstruction of a defect. The senior author, who has briefly reviewed complication rates in previous published literature, prefers the transverse lumbar artery perforator (TLAP) flap for reconstruction following pilonidal sinus excision in the intergluteal region. This paper illustrates the operative approach used by the senior author when raising a TLAP flap.     

Limited root repair in acute type A aortic dissection is safe but results in increased risk of reoperation

Objective

Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection.