Hyperbaric oxygen therapy in a patient with autosomal dominant polycystic kidney disease with a perinephritic abscess

A 68-year-old female in hemodialysis due to autosomal dominant polycystic kidney disease underwent resection of cysts in her right kidney via a laparoscopic approach due to abdominal pain. Three weeks after surgery, she was admitted with sepsis. A CT scan showed a large abscess around the right kidney. Percutaneous drainage of abscess was performed. The pus smear showed Gram-positive cocci and the culture contained methicillin-resistant Staphylococcus aureus. Ciprofloxacin, clindamycin and vancomycin were given. In the 3 weeks following admission, she remained febrile and septic and showed a progressive deterioration in her general condition, along with malnutrition and persistent drainage of purulent material from her right flank. The antibiotic therapy was changed to vancomycin, metronidazole and meropenem, but no improvement was observed. Because of the high risk associated with carrying out an open nephrectomy, we decided to use hyperbaric oxygen therapy (HBOT) as a potentially useful measure to control her infection. The patient underwent 26 daily sessions of 100% hyperbaric oxygen (2.5 atm). The use of HBOT induced a notable break in the clinical course of this patient’s retroperitoneal infection. She was discharged after day 58 without any signs of inflammatory activity, and she has not presented reactivation of infection since then. We think that this case suggests that this therapy could be a new therapeutic tool in the management of patients with similar clinical features when all other therapeutic measures have failed. We did not find any other reports of the use of HBOT in infections of renal cysts.     

Oxidative stress signaling underlying liver disease and hepatoprotective mechanisms

Oxidative stress is a redox imbalance between pro-oxidants and antioxidants in favour of the former ones, leading to different responses depending on the level of pro-oxidants and the duration of the exposure. In this article, we discuss the damaging or cytoprotective signaling mechanisms associated with oxidative stress by addressing (1) the role of prolonged and severe oxidative stress and insulin resistance as determinant factors in the pathogenesis of non-alcoholic fatty liver disease associated with obesity, which, with the concurrence of nutritional factors, may determine the onset of fatty liver and its progression to steatohepatitis; and (2) the development of an acute and mild pro-oxidant state by thyroid hormone administration, which elicits the redox up-regulation of the expression of proteins affording cell protection, as a preconditioning strategy against ischemia-reperfusion liver injury.     

Experimental infection of akodon molinae (Rodentia,Cricetidae) with Junín virus

Experimental infection with the XJ-Clone 3 strain of Junín virus in laboratory bred Akodon molinae, a cricetid rodent inhabiting the borders of endemic Argentine hemorrhagic fever areas, was studied. Suckling animals inoculated intracerebrally proved sensitive and became chronically infected. Sixty percent of the rodents showed neurologic involvement, with mortality reaching 60%. Virus was recovered from the brain at 7, 15, 21, 37, and 57 days postinfection (pi). By immunofluorescence (IF), viral antigens were observed up to 182 days pi in cells of the central nervous system (CNS). Concurrently, immunoglobulin deposits were detected in infected CNS cells from 21 up to 182 days pi. These deposits increased with the progression of the immune response as measured by IF antibodies. The detection of immune complexes in brain cells of apparently healthy animals suggests that neither viral replication nor the development of a humoral immune response are necessary requisites for neurovirulence in this host. Infection of adult rodents by different routes failed to induce disease or mortality and virus could not be recovered from oral swabs, blood, or organs. Our data suggest that Akodon molinae could play a role in nature as an alternative reservoir of Junín virus in addition to the main reservoir, Calomys musculinus.     

Clinical and epidemiologic characteristics of respiratory syncytial virus subgroups A and B infections in Santa Fe, Argentina

Respiratory Syncytial Virus (RSV) has two major antigenic groups, A and B. The implications of these variants in the epidemiology and pathogenesis of RSV infection are not well defined. This study was undertaken to compare the two RSV subgroups in patients admitted to hospital. Clinical and epidemiologic features of RSV subgroups in children under 30 months of age with proven RSV acute lower respiratory infections were examined during 4 winters from 1993 to 1996 in Santa Fe, Argentina. RSV typing was carried out with monoclonal antibodies in nasopharyngeal cells by indirect immunofluorescence. Of the 177 RSV positive nasopharyngeal aspirates obtained from 1993 to 1996, 85 (48%) were available for typing. Seventy-three (85.9%) specimens were identified as Subgroup A and 12 (14.1%) as Subgroup B. Except in 1993, in which only Subgroup A was detected, both variants circulated throughout the epidemic season. Subgroup A infections produced more severe disease than Subgroup B infections, as assessed by the length of the hospital stay and the use of respiratory support. This difference was age related, being evident in infants 0-6 months old. Patients with Subgroup B infections were also significantly less frequently breast-fed (95% vs. 75% for A and B subgroups, respectively; P = 0.04). It is concluded that the severity of disease in Argentinian patients admitted with acute RSV infections may be associated with Subgroup A strains as determined by a serogrouping method.     

Respiratory syncytial virus: changes in prevalence of subgroups A and B among Argentinian children, 1990-1996

The frequency of respiratory syncytial virus (RSV) and the distribution of subgroups A and B strains during 7 consecutive years (1990-1996) were examined in two cities of Argentina. Nasopharyngeal aspirates from 1,304 children less than 2 years of age hospitalized with acute lower respiratory infection were studied by indirect immunofluorescence. RSV was detected in 352 cases (26.9%), and the peak activity was observed in midwinter. Subgroup characterization was performed with two monoclonal antibodies against the F protein on nasopharyngeal aspirate smears. Of 195 samples, 174 (89.2%) were identified as subgroup A strains and 21 (10.8%) as subgroup B. Both strains cocirculated during 5 of 7 years studied with subgroup A predominating. Subgroup A occurred at least 8 times as often in all years except for 1994-1995. Children infected by subgroup A were younger than those infected by subgroup B (P < 0.05). The association of subgroup A infection with bronchiolitis and subgroup B with pneumonia was statistically significant (P < 0.03).     

PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase-amyloid complexes, amyloid25-35 fragment, glutamate, and hydrogen peroxide.

This work addresses the differential effects of several oxidative insults on two neuronal cell lines, PC12 and Neuro 2a cells, extensively used as neuronal models in vitro. We measured cellular damage using the cytotoxic assays for MTT reduction and LDH release and found that acetylcholinesterase (AChE)-amyloid-beta-peptide (Abeta) complexes, Abeta25-35 fragment, glutamate and H2O2 were over 200-fold more toxic to PC12 than to Neuro 2a cells. 17alpha and 17beta estradiol were able to protect both cell types from damage caused by H2O2 or glutamate. By contrast, other insults not related to oxidative stress, such as those caused by the nonionic detergent Triton X-100 and serum deprivation, induced a similar level of damage in both PC12 and Neuro 2a cells. Considering that the Abeta peptide, H2O2 and glutamate are cellular insults that cause an increase in reactive oxygen species (ROS), the intracellular levels of the antioxidant compound, glutathione were verified. Neuro 2a cells were found to have 4- to 5-fold more glutathione than PC12 cells. Our results suggest that Neuro 2a cells are less susceptible to exposure to AChE-Abeta complexes, Abeta25-35 fragment, glutamate and H2O2 than PC12 cells, due to higher intracellular levels of antioxidant defense factors.     

N-3 Polyunsaturated Fatty Acids and Their Lipid Mediators as A Potential Immune–Nutritional Intervention: A Molecular and Clinical View in Hepatic Disease and Other Non-Communicable Illnesses

In recent years, the beneficial effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) intake on human health has been widely accepted in the field of immunonutrition. Today, we find a diversity of supplements based on n-3 PUFAs and/or minerals, vitamins and other substances. The main objective of this review is to discuss the importance of n-3 PUFAs and their derivatives on immunity and inflammatory status related to liver disease and other non-communicable illnesses. Based on the burden of liver diseases in 2019, more than two million people die from liver pathologies per year worldwide, because it is the organ most exposed to agents such as viruses, toxins and medications. Consequently, research conducted on n-3 PUFAs for liver disease has been gaining prominence with encouraging results, given that these fatty acids have anti-inflammatory and cytoprotective effects. In addition, it has been described that n-3 PUFAs are converted into a novel species of lipid intermediaries, specialized pro-resolving mediators (SPMs). At specific levels, SPMs improve the termination of inflammation as well as the repairing and regeneration of tissues, but they are deregulated in liver disease. Since evidence is still insufficient to carry out pharmacological trials to benefit the resolution of acute inflammation in non-communicable diseases, there remains a call for continuing preclinical and clinical research to better understand SPM actions and outcomes.     

Short communication: high effectiveness of etravirine in routine clinical practice in treatment-experienced HIV type 1-infected patients

The effectiveness of etravirine has not been thoroughly investigated in routine clinical practice, where adherence rates and the heterogeneous nature of patients differ from the clinical trial setting. We evaluated the effectiveness of rescue regimens containing etravirine and the factors associated with treatment response. Multicenter retrospective cohort of all consecutive patients was recruited in a routine clinical practice setting. Patients were taking rescue regimens containing etravirine plus an optimized background regimen. The primary endpoint was the percentage of patients with HIV-1 RNA <50 copies/ml at week 48. The secondary endpoints were those factors associated with treatment response to etravirine. Endpoints were evaluated using univariate and multivariate analysis. A total of 122 patients were included with a median viral load of 11,938 (1055-55,500) copies/ml at baseline. The most frequent drugs in the backbone were darunavir/ritonavir in 98 (80.3%) patients and raltegravir in 76 (62.3%). In the full dataset analysis, 73% (89/122; 95% CI, 64-81%) of patients responded to treatment at week 48; in the on-treatment analysis, 82% (89/109; 95% CI, 71-87%) responded. The factors associated with treatment failure to etravirine [HR (95% CI)] were baseline CD4(+) T cell count <200 cells/mm(3) [2.45 (1.17-5.16)] and use of raltegravir [0.47 (0.22-0.99)] and darunavir [0.45 (0.21-0.98)] as backbone drugs. Skin rash was the only adverse event directly related to etravirine and led to withdrawal in three patients (2.5%). In routine clinical practice, rescue ETR-containing regimens are well tolerated and achieve rates of virological suppression higher than those observed in its pivotal clinical trials, especially when combined with darunavir and raltegravir.     

T3-induced liver AMP-activated protein kinase signaling: Redox dependency and upregulation of downstream targets

AIM: To investigate the redox dependency and promotion of downstream targets in thyroid hormone (T₃)-induced AMP-activated protein kinase (AMPK) signaling as cellular energy sensor to limit metabolic stresses in the liver. METHODS: Fed male Sprague-Dawley rats were given a single ip dose of 0.1 mg T₃/kg or T₃ vehicle (NaOH 0.1 N; controls) and studied at 8 or 24 h after treatment. Separate groups of animals received 500 mg N-acetylcysteine (NAC)/kg or saline ip 30 min prior T₃. Measurements included plasma and liver 8-isoprostane and serum β-hydroxybutyrate levels (ELISA), hepatic levels of mRNAs (qPCR), proteins (Western blot), and phosphorylated AMPK (ELISA). RESULTS: T₃ upregulates AMPK signaling, including the upstream kinases Ca²⁺-calmodulin-dependent protein kinase kinase-β and transforming growth factor-β-activated kinase-1, with T₃-induced reactive oxygen species having a causal role due to its suppression by pretreatment with the antioxidant NAC. Accordingly, AMPK targets acetyl-CoA carboxylase and cyclic AMP response element binding protein are phosphorylated, with the concomitant carnitine palmitoyltransferase-1α (CPT-1α) activation and higher expression of peroxisome proliferator-activated receptor-γ co-activator-1α and that of the fatty acid oxidation (FAO)-related enzymes CPT-1α, acyl-CoA oxidase 1, and acyl-CoA thioesterase 2. Under these conditions, T₃ induced a significant increase in the serum levels of β-hydroxybutyrate, a surrogate marker for hepatic FAO. CONCLUSION: T₃ administration activates liver AMPK signaling in a redox-dependent manner, leading to FAO enhancement as evidenced by the consequent ketogenic response, which may constitute a key molecular mechanism regulating energy dynamics to support T₃ preconditioning against ischemia-reperfusion injury.