Epilepsy is a neurological disease with high global prevalence. Despite the range of drug-based treatments currently available to control the condition, one in 3 patients experiences epileptic seizures. Therapeutic alternatives for these patients include the ketogenic diet, surgery or the cerebral implantation of neurostimulators; however these are benefits with limits. The target of this study is to find a new complementary treatment for these patients, studying the effectiveness of probiotics for controlling epileptic seizures in patients with drug-resistant epilepsy. A prospective study was designed in which a group of patients with drug-resistant epilepsy was administered a probiotic mixture for 4 months. Patients were assessed before and after taking the probiotics; among other variables, number of seizures and patients' quality of life (QOLIE-10) were monitored. Levels of cD-14, interleukin 6, and γ-aminobutyric acid were also analysed throughout the study. 45 patients were included in the study. In an intention-to-treat analysis, 28.9% of all patients displayed a greater than 50% reduction in the number of seizures (the parameter required in clinical trials). A significant improvement was also observed in patients' quality of life. We found that probiotics may be an option for supplementary therapy. Since the use of probiotics is safe, they may contribute to improving seizure control, and therefore quality of life, in patients with drug-resistant epilepsy. The study has been registered in https://clinicaltrials.gov with number NCT03403907.
Chronic liver disease may result in a sequential progression through fibrosis, cirrhosis and lead, eventually, to hepatocellular carcinoma (HCC). Hepatic stellate cells (HSC) seem to be responsible for the fibrogenic response through the activation of an autocrine loop involving the chemokine receptor, CCR5. However, the role of CCR5 in HCC remains poorly understood. Since this receptor is also one of the main ports of entry for the human immunodeficiency virus (HIV), several CCR5 inhibitors are being used in the clinic to reduce viral load. We used one of these inhibitors, maraviroc (MVC), in a mouse model of diet-induced HCC to investigate whether this intervention would reduce disease progression. Animals treated with MVC on top of a normal control diet did not present any evidence of toxicity or any morphological change when compared with non-treated mice. Animals treated with MVC presented higher survival, less liver fibrosis, lower levels of liver injury markers and chemokines, less apoptosis, lower proliferation index, and lower tumor burden than their counterparts receiving only the hepatotoxic diet. In addition, MVC inhibits HSC activation markers such as phosphorylation of p38 and ERK, and increases hepatocyte survival. This study suggests that MVC, a well tolerated and clinically characterized drug, may be used as a preventative treatment for HCC. Clinical studies are needed to demonstrate the efficacy of this drug, or other CCR5 inhibitors, in patients with high risk of developing HCC.
Highly active antiretroviral therapy (HAART) has considerably improved the prognosis of HIV-infected patients. However, prolonged use of HAART has been related to long-term adverse events that can compromise patient health such as HIV-associated lipodystrophy syndrome (HALS) and nonalcoholic fatty liver disease (NAFLD). There is consistent evidence for a central role of mitochondrial dysfunction in these pathologies. Nucleotide reverse transcriptase inhibitors (NRTIs) have been described to be mainly responsible for mitochondrial dysfunction in adipose tissue and liver although nonnucleoside transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) have also showed mitochondrial toxicity, which is a major concern for the selection and the long-term adherence to a particular therapy. Several mechanisms explain these deleterious effects of HAART on mitochondria, and evidence points to other mechanisms beyond the “Pol-γ hypothesis.” HIV infection has also direct effects on mitochondria. In addition to the negative effects described for HIV itself and/or HAART on mitochondria, HIV-infected patients are more prone to develop a premature aging and, therefore, to present an increased oxidative state that could lead to the development of these metabolic disturbances observed in HIV-infected patients.
This study describes the epidemiological, clinical, and microbiological characteristics of a new tick-borne disease in SpainDermacentor-borne necrosis erythema lymphadenopathy (DEBONEL). The clinical presentations include an eschar at the site of the tick bite, surrounded by an erythema and painful regional lymphadenopathy. The disease appears during the colder months and its vector is Dermacentor marginatus (D. marginatus). From January 1990 to December 2004, 54 patients presented at Hospital of La Rioja with these clinical and epidemiological data. The ratio of females to males was 32/22. The average age was 37 years. In all cases tick bites were located on the upper body (90% on the scalp). The median incubation period was 4.7 days. Signs and symptoms were mild in all cases. Only a small number of patients presented mild and nonspecific abnormalities in a complete blood cell count and mild elevation of erythrocyte sedimentation rates and C-protein reactive and liver enzyme levels. Serological evidence of acute rickettsiosis was observed in 19 patients (61%). In 29% sera tested by polymerase chain reactions (PCRs) were positive. The sequence obtained from a PCR product revealed 98% identity with Rickettsia sp. strains RpA4, DnS14, and DnS28. All ticks removed from patients were PCR-positive. Sequencing showed 8 of them identified as R. slovaca and 2 as Rickettsia sp. strains RpA4, DnS14, and DnS28.
The first cluster of cases of human Rickettsia felis infection in Spain diagnosed by PCR is reported. CASE REPORTIn September 2005, a 26-year-old woman with fever (38°C) and skin lesions and her 30-year-old husband were evaluated in our hospital. She felt unwell and began with itching skin lesions, mainly located on flexion areas of the lower extremities. On examination, she had fever, malaise, arthralgia, and pruritic papular rash over the lower extremities, abdomen, and chest. He showed the same clinical picture, although fever was absent. No other symptoms or signs were observed. Both patients and their dog had visited a forest area on the northwest of La Rioja (known as "Alto de Piqueras") 2 days previously. The dog was afebrile but symptomatic (fatigue, vomiting, and diarrhea). Multiple red points identified as chiggers (larvae of trombiculid mites, Neotrombicula autumnalis) were observed over the dog. At that time, neither ticks nor fleas were found. Nevertheless, fleas had parasitized the dog, and both patients said they had been bitten by fleas. No exposure to cats was mentioned. According to our previous experience, a presumptive diagnosis of human trombiculiasis was made. Over the last 5 years, we have diagnosed seasonal outbreaks of this disease in people who have visited the putative forest area in autumn and have presented with this itching rash (6). Nevertheless, a prospective protocol for vector-borne diseases, which included the main tick and flea-borne infections endemic in Spain (Lyme borreliosis, Bartonella infections, human anaplasmosis, Q fever and spotted fever group [SFG], and typhus group [TG] rickettsioses), was followed.Laboratory investigations showed slightly elevated liver enzymes. The values for the female patient were as follows: aspartate amino transferase, 50 IU/liter; alanine amino transferase, 45 IU/liter; and lactate dehydrogenase, 456 IU/liter. C-reactive protein was elevated (15 mg/liter; normal, Ͻ10), and the remaining biochemical values were normal. The values for the male patient were as follows: aspartate amino transferase, 39 IU/liter; alanine amino transferase, 42 IU/liter; gamma-glutamyl-transpeptidase, 79 IU/liter; and lactate dehydrogenase, 498 IU/liter. The numbers of leukocytes, platelets, and erythrocytes were normal for both patients.Serologic testing for Lyme borreliosis, cat-scratch disease, human anaplasmosis, and Q fever, as well as SFG and TG rickettsioses (immunoglobulin G [IgG] enzyme-linked immunosorbent assays and Western blotting for Lyme borreliosis and IgG indirect immunofluorescence assays for the remaining ones) were negative for both patients. DNA was extracted from the human acute blood-EDTA and serum specimens and also from a dog serum sample (all before antibiotic therapy) by using a blood DNA spin kit (Genomed; Genycell Biotech España, S.L., Granada, Spain) according to the manufacturer's instructions. These extracts were used as templates in PCRs to investigate the arthropod-borne diseases above indicated (Table 1). Due to the low sensitivity...
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