Africane-type sesquiterpenoids from the Argentine liverwort Porella swartziana and their antibacterial activity

Seven africanes (1, 2a,b, 3-6), two of them new (1, 2a), three secoafricanes (7-9), one of them new (7), and two norsecoafricanes (10, 11a), one of them new (10), all of them swartzianin-type, have been isolated from an Argentine collection of the endemic liverwort Porella swartziana. The structures of the new compounds were established by extensive 1D and 2D NMR spectroscopic data. Absolute configurations of compounds 2a, 2b, and 10 were derived on the basis of CD spectra. The compounds were tested for activity against a variety of microbes, but none were found to exhibit significant antibacterial activity.     

Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus–infected rhesus macaques on antiretroviral therapy

Proliferation of latently infected CD4⁺ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4⁺ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA–treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4⁺ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.     

Long-term results of elective hepatectomy for the treatment of ruptured hepatocellular carcinoma

Background/Purpose According to the General rules for the clinical and pathological study of primary liver cancer, compiled by the Liver Cancer Study Group of Japan, ruptured hepatocellular carcinoma (HCC) is classified as stage 4, even if the tumor is small and solitary. We examined the long-term results of elective hepatectomy for the treatment of ruptured HCC. Methods A first hepatectomy was performed without operative death in 193 patients with HCC. Ten patients had ruptured HCC (ruptured group) and 183 patients had nonruptured HCC (nonruptured group). The extension of HCC was macroscopically classified as stage 1 in 23 patients, stage 2 in 71, stage 3 in 53, and stage 4 in 46. Results Cumulative survival rates in the ruptured group at 1, 5, and 10 years were 90.0%, 67.5%, and 20.3%, respectively. The cumulative survival rate was lower in patients with stage 4 disease in the nonruptured group than that in patients in the ruptured group (P < 0.05). Cumulative survival rates did not differ significantly between patients in the ruptured group and those with stage 2 or stage 3 disease. Conclusions Survival rates after elective hepatectomy in patients with ruptured HCC are good, even if the disease is classified as stage 4.     

Un tratamiento nuevo para una enfermedad antigua: tratamiento de la hipertensión arterial resistente mediante denervación simpática renal percutánea

Hypertension is a major contributor to cardiovascular events, such as stroke and myocardial infarction, with accelerated sympathetic nerve activity implicated in its pathogenesis. However, hypertension in many patients is not adequately controlled, despite the availability of numerous medication classes. Novel procedure—as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation therapy—have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation delivers not only a decrease in blood pressure levels but also renal as well as systemic sympathetic nerve activity. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which implies no counterregulatory mechanism or re-innervation of afferent renal sympathetic nerve so far. Renal sympathetic denervation is expected to be a promising treatment for patients with hypertension, congestive heart failure, chronic kidney disease, and metabolic syndrome implicated in the pathogenesis of potentiated sympathetic nerve activity. This review will focus on the current devices and procedures, their outcomes and prospects in the treatment of hypertension.     

Accurate diagnosis and treatment of Vibrio vulnificus infection: a retrospective study of 12 cases

Background and aimsVibrio vulnificus causes an infectious disease that has extremely poor convalescence and leads to necrotic fasciitis. In this study, we sought to define the characteristic epidemiology of V. vulnificus infection and clarify its diagnosis at the global level.MethodsOver a period of 10 years, we investigated the appearance of symptoms, underlying conditions, treatment, and mortality in 12 patients (eight men, four women; >50 years old; average age, 66 years,) infected with V. vulnificus.ResultsThe development of symptoms occurred primarily between June and September, a period during which seawater temperature rises and the prevalence of V. vulnificus increases. All patients had underlying diseases, and seven patients reported a history of consuming fresh fish and uncooked shellfish. The patients developed sepsis and fever with sharp pain in the limbs. Limb abnormalities were observed on visual examination. All patients underwent debridement; however, in the survival group, the involved limb was amputated early in 80% patients. The mortality rate was 58.3%.ConclusionRecognition of the characteristic epidemiology and clinical features of this disease is important, and positive debridement should be performed on suspicion. When the illness reaches an advanced stage, however, amputation should be the immediate treatment of choice.     

Sex difference in the biliary excretion of digoxin and its metabolites in aging Wistar rats

The biliary excretion of digoxin (Dg3) and its metabolites was studied in both young (3-month-old) and old (25- and 30-month-old) Wistar rats of both sexes. The 2 h biliary recovery (% of the dose) of intravenously injected [3H]Dg3 (0.01 mg/100 g) radioactivity was similar between young male and female rats, while the first 10 min excretion was significantly higher in females. In old (25-month-old) male rats, the 2 h biliary recovery of radioactivity was significantly lower than the corresponding young value. This was primarily due to the drastic decrease with age in excretion of bis-digitoxoside. On the other hand, in old female rats (25- and 30-month-old) the 2 h recovery value was not significantly different from the corresponding young (3-month-old) value. This was due to the much higher percentage (more than 80% of the total) of Dg3 in the female bile radioactivity which did not significantly decrease with age. The results suggest that the rate of stepwise cleavages of the sugar chain of Dg3 decreases with age more rapidly in male than in female rats as has been previously shown by the authors for digitoxin. Large sex differences observed in the age-dependent alteration in Dg3 metabolism and its biliary excretion raise a caution against a generalization of the data obtained from a single sex in this animal species with regard to the effect of aging.     

Autogenous bone peg fixation for osteochondritis dissecans of the elbow

Objectives  

Restoration of pain-free elbow function and prevention of osteoarthritis in patients with osteochondritis dissecans treated with autogenous bone peg fixation.