Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the alpha(1)-adrenergic vasoconstrictor methoxamine and the mechanisms involved in its regulation. A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX) inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ 29,548. TXA(2) production, COX-1 and COX-2 mRNA expression, and immunostaining for TXA(2) synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to methoxamine associated with overexpression of COX-2 and TXA(2) synthase as well as with increased production of TXA(2). The hyperresponse to methoxamine of cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to methoxamine. In conclusion, COX-derived prostanoids, mainly TXA(2), play a major role in regulating the response of cirrhotic livers to methoxamine.     

Quality indicators and specifications for strategic and support processes in laboratory medicine

BACKGROUND: This work is the second part of a study regarding indicators and quality specifications for the non-analytical processes in laboratory medicine. Five primary care and five hospital laboratories agreed on the indicators for two strategic processes (quality planning and project development) and various support processes (client relationships, instrument and infrastructure maintenance, safety and risk prevention, purchases and storage, personnel training). METHODS: In the majority of cases, the median values recorded over 1 year is considered to be the state-of-the-art in our setting and proposed as the quality specification for the indicators stated. Values have been stratified according to primary care and hospital laboratory for referred tests and group of personnel for training. In some cases, the specifications have been set equal to zero events, such as serious incidents in the infrastructure maintenance process and number of work accidents in the safety and risk prevention process. RESULTS AND CONCLUSIONS: In light of this study, an effort is needed to optimize decisions regarding corrective actions and to move from a subjective individual criterion to systematic and comparative management. This preliminary study provides a comprehensive vision of a subject that could motivate further research and advances in the quality of laboratory services.     

Effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia 21 years after its introduction

Hepatitis B is a viral disease of global importance. In Catalonia in the 1980s, the seroepidemiological pattern of HBV infection was low-intermediate. In 1990, the Expert Committee on Vaccinations of the Department of Health of the Generalitat of Catalonia evaluated the systematic introduction of hepatitis B vaccination in preadolescents, maintaining the vaccination of risk groups. The objective of this study was to estimate the effectiveness and impact of the systematic hepatitis B vaccination programme in preadolescents in Catalonia 21 years after its introduction. A retrospective cohort study was conducted, comparing the disease incidence in vaccinated and unvaccinated cohorts. Cases of hepatitis B were defined as those reported by the General Subdirectorate of Surveillance and Response to Public Health Emergencies between 2000 and 2014. The incidence rate was 2.5 per 100,000 persons in 1991 and 1.2 per 100,000 persons in 2014, a reduction of 52%. During the study period, 388 cases of hepatitis B infection were notified, of which three were classified as vaccine failures. Vaccine effectiveness was 99.30% (95% CI: 97.83–99.78) and the population prevented fraction in the cohorts of preadolescents studied was 64.56% (95% CI: 60.45–68.66). The effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia is high, with the consequent benefits for the population.     

Morphofunctional responses to anaemia in rat skeletal muscle

Adult male Sprague-Dawley rats were randomly assigned to two groups: control and anaemic. Anaemia was induced by periodical blood withdrawal. Extensor digitorum longus and soleus muscles were excised under pentobarbital sodium total anaesthesia and processed for transmission electron microscopy, histochemical and biochemical analyses. Mitochondrial volume was determined by transmission electron microscopy in three different regions of each muscle fibre: pericapillary, sarcolemmal and sarcoplasmatic. Muscle samples sections were also stained with histochemical methods (SDH and m-ATPase) to reveal the oxidative capacity and shortening velocity of each muscle fibre. Determinations of fibre and capillary densities and fibre type composition were made from micrographs of different fixed fields selected in the equatorial region of each rat muscle. Determination of metabolites (ATP, inorganic phosphate, creatine, creatine phosphate and lactate) was done using established enzymatic methods and spectrophotometric detection. Significant differences in mitochondrial volumes were found between pericapillary, sarcolemmal and sarcoplasmic regions when data from animal groups were tested independently. Moreover, it was verified that anaemic rats had significantly lower values than control animals in all the sampled regions of both muscles. These changes were associated with a significantly higher proportion of fast fibres in anaemic rat soleus muscles (slow oxidative group = 63.8%; fast glycolytic group = 8.2%; fast oxidative glycolytic group = 27.4%) than in the controls (slow oxidative group = 79.0%; fast glycolytic group = 3.9%; fast oxidative glycolytic group = 17.1%). No significant changes were detected in the extensor digitorum longus muscle. A significant increase was found in metabolite concentration in both the extensor digitorum longus and soleus muscles of the anaemic animals as compared to the control group. In conclusion, hypoxaemic hypoxia causes a reduction in mitochondrial volumes of pericapillary, sarcolemmal, and sarcoplasmic regions. However, a common proportional pattern of the zonal distribution of mitochondria was maintained within the fibres. A significant increment was found in the concentration of some metabolites and in the proportion of fast fibres in the more oxidative soleus muscle in contrast to the predominantly anaerobic extensor digitorum longus.     

Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPP<Superscript>+</Superscript> Toxicity In Vivo

Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP⁺) produces similar biochemical changes in rat to those seen in Parkinson’s disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP⁺ lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress. In the present study, pretreatment with the intraperitoneal injection of Hc-TeTx in rats prevents the decrease of tyrosine hydroxylase immunoreactivity in the striatum due to injury with MPP⁺, when applied stereotaxically in the striatum. Similarly, striatal catecholamine contents are restored, as well as the levels of two other dopaminergic markers, the dopamine transporter (DAT) and the vesicular monoamine transporter-2 (VMAT-2). Additionally, uptake studies of [³H]-dopamine and [³H]-MPP⁺ reveal that DAT action is not affected by Hc-TeTx, discarding a protective effect due to a reduced entry of MPP⁺ into nerve terminals. Behavioral assessments show that Hc-TeTx pretreatment improves the motor skills (amphetamine-induced rotation, forelimb use, and adjusting steps) of MPP⁺-treated rats. Our results lead us to consider Hc-TeTx as a potential therapeutic tool in pathologies caused by impairment of dopaminergic innervation in the striatum, as is the case of PD.     

Frequent detection of monkeypox virus DNA in saliva,semen, and other clinical samples from 12 patients,Barcelona, Spain,May to June 2022

A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples collected at different time points from 12 patients by real-time PCR. MPX DNA was detected in saliva from all cases, sometimes with high viral loads. Other samples were frequently positive: rectal swab (11/12 cases), nasopharyngeal swab (10/12 cases), semen (7/9 cases), urine (9/12 cases) and faeces (8/12 cases). These results improve knowledge on virus shedding and the possible role of bodily fluids in disease transmission.