The main goal of this article is to update etiology, epidemiology, diagnosis, treatment and outcome of the various causes of mesenteric ischemia in order to elucidate its labyrinthine clinical riddle, by reviewing the current English medical literature. Mesenteric ischemia is a quite uncommon disorder, observed in the emergency department. It is a life-threatening vascular emergency that requires early diagnosis and intervention to restore mesenteric blood flow and to prevent bowel necrosis and patient death. Consequently, it is a vital diagnosis to make because of its high mortality rate and its thorny complications. The underlying causes vary, and the prognosis depends on the specific findings during clinical examination. Vague and nonspecific clinical findings and limitations of diagnostic studies make the diagnosis a significant challenge. The prognosis of acute mesenteric ischemia of any type is grave. The complications following this medical jigsaw puzzle are also severe. Patients in whom the diagnosis is missed until infarction occurs have a mortality rate of 90%. Even with good treatment, up to 50-80% of patients die. Survivors of extensive bowel resection face lifelong disability. Despite the progress in understanding the pathogenesis of mesenteric ischemia and the development of treatment modalities, the entity remains a diagnostic challenge for clinicians. Delay in diagnosis contributes to a high mortality rate. Early diagnosis and adequate treatment can improve the clinical outcome. Even if diagnostic modalities have improved since the first successful attempts to confront effectively this clinical entity, mesenteric ischemia still remains a lethal diagnostic enigma for the medical community.
It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-α or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log10 and 3.1log10 copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C.
Serum gamma-glutamyl transferase (GGT) activity is a general clinical marker of excessive alcohol consumption, and GGT reflects changes in oxidative stress and implicated in the progression of hypertension. Recent guidelines classify persons with above-optimal blood pressure (BP) but not clinical hypertension as having prehypertension for a systolic BP (SBP) of 120 to 139 mmHg and/or a diastolic BP (DBP) of 80 to 89 mmHg; however, only limited data are available on the association between serum GGT and this entity among community-dwelling men in Japan. We performed a cross-sectional study to examine whether serum GGT was associated with prehypertension. Study participants (754 men, age 56 ± 15 years) without a clinical history of stroke, transient ischemic attack, myocardial infarction, angina, or renal failure were recruited from a single community. Thirty-seven percent of participants had prehypertension and 39.3% had hypertension. Multiple regression analysis using SBP and DBP as objective variables, adjusted for risk factors as explanatory variables, showed that log GGT was significantly and independently associated with elevated SBP (β = 0.109, P = 0.006) and DBP (β = 0.238, P < 0.001). Compared with participants in the lowest tertile of serum GGT (< 29 IU/L), the multivariate-adjusted odds ratio (OR) (95% CI) for prehypertension was 1.73 (1.06-2.81) for the middle tertile (29-53 IU/L) and 2.37 (1.31-4.31) for the highest tertile (> 53 IU/L). Moreover, the respective ORs for hypertension were 1.82 (1.04-3.18) and 3.11 (1.61-6.03). These results suggest that higher serum GGT levels are associated with prehypertension or hypertension in the general male population.
Diabetic patients have a decreased incidence of acute respiratory distress syndrome, but the mechanism responsible for the decreased incidence is uncertain. Reabsorption of alveolar edema fluid (alveolar fluid clearance) has been considered to play an important role in resolution of acute respiratory distress syndrome. However, little is known regarding alveolar fluid clearance in diabetes mellitus. Since the obese Zucker rat has been used as an experimental model for diabetes mellitus, we determined if alveolar fluid clearance increased in the obese Zucker rat. First, we compared alveolar fluid clearance in obese Zucker rats with that in lean Zucker rats and Sprague-Dawley (SD) rats. Then, we determined the role of sodium channel, Na,K-ATPase, and β2-adrenoceptor, which drives alveolar fluid clearance, in obese Zucker rats. Alveolar fluid clearance was estimated by the progressive increase in alveolar albumin concentrations in the isolated lungs. We found that basal alveolar fluid clearance in obese Zucker rats was two-fold greater than that in lean Zucker rats and SD rats. The mRNA expression of α1-, β1-Na, K-ATPase and β2-adrenoceptor, but not mRNA expression of sodium channel, increased in obese Zucker rats. A selective β2-agrenergic antagonist, but not a Na, K-ATPase inhibitor, specifically inhibited the increase in alveolar fluid clearance in obese Zucker rats. These results indicate that overexpression of β2-adrenoceptor primarily increases basal alveolar fluid clearance in the obese Zucker rat. We speculate that the stimulation of alveolar fluid clearance ameliorates acute respiratory distress syndrome in patients with diabetes mellitus.
Tyrosinase is a mono-oxygenase with a dinuclear copper catalytic center which is able to catalyze both the ortho-hydroxylation of monophenols (cresolase activity) and the oxidation of catechols (catecholase activity) yielding ortho-quinone products. Tyrosinases appear to have arisen early in evolution and are widespread in living organisms where they are involved in several processes, including antibiosis, adhesion of molluscs, the hardening of the exoskeleton of insects, and pigmentation. Tyrosinase is the principal enzyme of melanin formation in vertebrates and is of clinical interest because of the possible utilization of its activity for targeted treatment of malignant melanoma. Tyrosinase is characterised by an irreversible inactivation that occurs during the oxidation of catechols. In a recent publication we proposed a mechanism to account for this feature based on the ortho-hydroxylation of catecholic substrates, during which process Cu(II) is reduced to Cu(0) which no longer binds to the enzyme and is eliminated (reductive elimination). Since this process is dependent on cresolase activity of tyrosinase, a strong prediction of the proposed inactivation mechanism is that it will not be exhibited by enzymes lacking cresolase activity. We show that the catechol oxidase readily extracted from bananas (Musa cavendishii) is devoid of cresolase activity and that the kinetics of catechol oxidation do not exhibit inactivation. We also show that a species with the molecular mass of the putative cresolase oxidation product is formed during tyrosinase oxidation of 4-methylcatechol. The results presented are entirely consistent with our proposed mechanism to account for suicide-inactivation of tyrosinase.
Various stresses can be followed by sudden unexpected deaths, and autopsies sometimes fail to identify pathological findings that determine the cause of death. Pathologists occasionally explain such deaths as being due to overstimulation of sympathoadrenal systems, but postmortem assessment of antemortem sympathoadrenal activity has not been established. An animal model of weight injuries was used to quantify sympathoadrenal response to contusion stress, which is common in forensic fields. A weight was dropped from a given height onto the right dorsal limb of each anesthetized rat, with a control group and three stress groups (n = 4, each): 1000 g-80 cm, 1000 g-40 cm, and 500 g-40 cm. To explore the postmortem changes, we also included ten groups comprised of control and 1000 g-80 cm groups, whose tissues were harvested during 12 hours after euthanasia. Real-time quantitative polymerase-chain reaction was performed to quantify relative expression levels of mRNAs for catecholamine biosynthetic enzymes in the adrenals and the anterocervical ganglia: tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). The expression levels of all target mRNAs in the adrenals increased with the intensity of impact (TH, p < 0.0005; DBH and PNMT, p < 0.005), and particularly, TH mRNA level exhibited near-stepwise elevation (p < 0.05). In contrast, no significant differences were detected in the anterocervical ganglia. Moreover, these mRNA levels in the adrenals decreased with increasing postmortem interval length. Thus, TH mRNA level may be a good marker of sympathoadrenal response to contusion stress during the early postmortem period.
Good compliance with hypoglycemic therapy is important for diabetes treatment, since positive relationship between medication compliance and glycemic control has been reported. To improve medication compliance, the oral disintegrating tablet technology that facilitates drug administration without water has been employed in various drugs, including voglibose, an alpha glucosidase inhibitor. In the present survey, we investigated safety profile of voglibose oral disintegrating tablet (VODT), and whether treatment with VODT results in improvement of medication compliance and glycemic control. Patients with diabetes received VODT 0.6 or 0.9 mg/day for 12 weeks. Among 2,930 eligible patients, adverse drug reactions were observed in 3.6%, with the most common being abdominal distension, flatulence, diarrhea, and increased alanine aminotransferase levels. In 1,067 patients who received conventional voglibose tablet (CVT) prior to VODT, 53.1% reported that taking VODT was easier than taking CVT. Medication compliance was improved after switching to VODT in 28.4% of patients who missed taking tablets more than one time a week during CVT treatment. A significant decrease in HbA1C levels was observed in patients whose medication compliance was improved after switching to VODT (P = 0.033), but there was no significant reduction in HbA1C levels in patients whose medication compliance did not change. In conclusion, the present survey suggests that the safety profile of VODT is comparable with that of CVT, and switching from CVT to VODT has positive impact on medication compliance which may lead to an improvement in glycemic control.
There is a concern that the widespread use of antiretroviral drugs to treat HIV infections may result in the increased transmission of a drug-resistant virus. Drug resistance testing before initiating treatment among newly diagnosed HIV patients is helpful in the design of initial regimens. Although HIV infected patients have been increasing in Korea, the transmission rate of drug-resistant HIV is unknown. The aim of this study was to determine the prevalence of antiretroviral drug resistance-associated mutations in patients newly diagnosed as early stage of HIV infection in Korea. We defined patients with early HIV infections as those with confirmed diagnoses who had an indeterminate Western blot. We performed genotypic resistance testing in 66 HIV-1 subjects at an early HIV infection stage who were identified between March 2002 and June 2005. Two of the 66 subjects with early HIV infections showed major mutations associated with resistance. Major mutations by themselves reduce susceptibility to one or more drugs and occur commonly during virological failure. Minor mutations have little or no effect on susceptibility and occur only after other drug-resistance mutations. The resistant mutation of reverse-transcriptase gene was found at E44D, and the major resistant mutation of protease gene was found at M46L. Minor protease resistance mutations were seen in 52 cases. Genetic subtype analysis revealed that all subjects were infected with HIV-1 subtype B. In conclusion, the prevalence of drug-resistant HIV-1 in patients newly diagnosed with HIV in its early infection stage is not high in Korea.
Endothelin is both a potent vasoconstrictor and an important mediator of ischemia-reperfusion (IR) injury. Therefore, the role of endothelin receptor antagonism in IR-induced-tissue injury carries great interest. Here, we examined the effect of tezosentan, a nonselective antagonist for endothelin receptors, on myocardial injury induced by abdominal aortic IR, which represents a model of the IR injury in distant organs frequently occurred after vascular surgery. Thirty-two Wistar rats were randomized into four groups (n = 8) as follows: control (sham laparotomy), aortic IR (120 min ischemia and 120 min reperfusion), aortic IR + tezosentan (10 mg/kg intravenous injection before ischemia plus continuous intravenous infusion of 1 mg/kg/hr during the IR injury), and control + tezosentan. Biochemical analysis showed that aortic IR significantly increased (p < 0.05 vs control) the plasma levels of troponin-I, interleukin-6 and tumor necrosis factor-alpha, and the myocardial tissue levels of malondialdehyde, superoxide dismutase and catalase, whereas tezosentan significantly decreased these same factors (p < 0.05 vs aortic IR). Histological evaluation also showed that aortic IR significantly increased (p < 0.05 vs control) myocardial disorganization, myofiber swelling and myofiber eosinophilia in myocardial tissue samples, whereas tezosentan significantly decreased these factors (p < 0.05 vs aortic IR). These results indicate that tezosentan has protective effects against myocardial injury induced by abdominal aortic IR in rats. We propose that the mechanisms underlying this protective effect of tezosentan involves the reduction of oxidative stress and subsequent lipid peroxidation, the inhibition of systemic inflammatory response, and acting cytoprotective on myocytes after aortic IR.
Vision contributes to upright postural control by providing afferent feedback to the cerebellum. Vision is generally classified into central and peripheral vision, but little is known about the respective role of central and peripheral vision for postural control with different visual acuity levels. This study examined the influence of visual acuity and visual field conditions on upright posture. Eleven males (21.1 ± 2.0 yrs) and 15 females (22.2 ± 2.2 yrs) were classified into high (above 1.0 binocular vision) and low (below 0.3) visual acuity groups. Postural sway was measured for 1 min in each of three visual field conditions (central vision, full vision, and no vision). Participants were given only central visual information (central vision), central and peripheral visual information (full vision), or no visual information (no vision). The effect of central vision on postural sway was detected as a difference between no vision and central vision conditions, and the effect of peripheral vision was assessed as a difference between central vision and full vision conditions. The low visual acuity group decreased their sway amplitude in antero-posterior direction using central plus peripheral visual information, but the high visual-acuity group did not. The high frequency sway was significantly smaller in the low visual-acuity group than that in the high visual-acuity group under the no vision and central vision conditions. These findings suggest the necessity of considering participants' visual acuity in examining the role of the visual information from the central and peripheral visual fields.