Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg- chronic hepatitis B patients: A 4-year study

Background and Aim:  Adefovir dipivoxil (ADV) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative (HBeAg^-) chronic hepatitis B (CHB). However, it is unclear whether LAM treatment should be continued in these patients. We aimed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg^- CHB.
Methods:  Sixty LAM-resistant patients with HBeAg^- CHB were randomly assigned (3:1) to combination therapy (10 mg ADV once daily plus ongoing LAM at 100 mg once daily [ n  = 45]) or 10 mg ADV monotherapy once daily ( n  = 15). Virological and biochemical responses were defined as hepatitis B virus (HBV)–DNA <400 copies/mL and as normalization of alanine aminotransferase levels, respectively.
Results:  The median follow-up time was 53 months (range 20–60 months). A virological response was observed in 38/45 (84.4%) and 11/15 (73.3%) patients in the ADV/LAM and ADV monotherapy groups, respectively ( P  = 0.56). Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group (90.9% vs 57.1%, respectively; P  = 0.01). In the ADV/LAM group, serum HBV–DNA remained undetectable in all patients who achieved a virological response ( n  = 38). In the ADV monotherapy group, virological breakthrough occurred in four of the 11 patients who achieved a virological response (36.4%; P  < 0.001 vs the ADV/LAM group, log–rank test). In addition, two patients in each group who did not achieve a virological response eventually developed ADV resistance.
Conclusions:  Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg^- CHB.     

Assessment of cerebral blood volume in schizophrenia: A magnetic resonance imaging study

Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia.     

Somatostatin increases rat locomotor activity by activating sst2 and sst4 receptors in the striatum and via glutamatergic involvement

The involvement of striatal somatostatin receptors (sst₁, sst₂ and sst₄) in locomotor activity was investigated. Male Sprague–Dawley rats, 280–350 g, received in the striatum bilateral infusions of saline, somatostatin, and selective sst₁, sst₂, and sst₄ ligands. Spontaneous locomotor activity was recorded for 60 min. The involvement of excitatory amino acid receptors (AMPA and NMDA) on somatostatin’s actions was also examined. Western blot analysis was employed for the identification of somatostatin receptors in striatal membranes. Somatostatin, sst₂ and sst₄, but not sst₁, selective ligands increased rat locomotor activity in a dose-dependent manner. Blockade of AMPA and NMDA receptors reversed somatostatin’s actions. In conclusion, striatal somatostatin receptor activation differentially influence rat locomotor activity, while glutamatergic actions underlie the behavioral actions of somatostatin.     

The impact of psychological functioning upon systemic sclerosis patients' quality of life

OBJECTIVE: To access health-related quality of life (HRQOL) in systemic sclerosis (SSc) patients using the World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF), and to identify the association between clinical, psychopathological, and personality parameters and SSc patients' HRQOL. METHODS: Fifty-six patients with SSc were compared with 72 patients with rheumatoid arthritis (RA), 43 with systemic lupus erythematosus (SLE), 34 with Sj?gren syndrome (SS), and 74 healthy controls. A wide range of clinical information was collected and the following self-report instruments were used: the WHOQOL-BREF, the General Health Questionnaire, the Symptom Distress Check List, the Hostility and Direction of Hostility Questionnaire, the Defense Style Questionnaire, and the Sense of Coherence scale. RESULTS: HRQOL perceived by SSc patients was significantly impaired compared with healthy controls. Initial examination of HRQOL across groups of rheumatology patients revealed similar HRQOL, but when age, pain, psychopathology, and coping strategies were taken into account, SSc patients had impaired physical health QOL in comparison with RA, SLE, and SS patients. Arthritis-related pain was closely associated with SSc patients' HRQOL. Elevated psychological distress symptoms as well as certain personality traits, such as maladaptive defenses and lower sense of coherence, were also associated with diminished HRQOL. CONCLUSIONS: Impaired psychological functioning is associated with diminished HRQOL in SSc, and consequently, treatment of depressive symptoms should be considered a priority. Moreover, assessment of HRQOL should only be used in conjunction with specific psychological distress measurements, to detect the influence of psychopathology on HRQOL.     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.     

Lipoprotein profile,glycemic control and physical fitness after strength and aerobic training in post-menopausal women with type 2 diabetes

We studied the effects on blood lipids and physical fitness after a training program that combined strength and aerobic exercise in postmenopausal women with type 2 diabetes. Ten patients (55.0 ± 5.2 years) followed four exercise sessions per week, two strength and two aerobic, and ten (59.4 ± 3.2 years) served as a control group. Lipid profile, glycated hemoglobin (HbA_1c), HOMA2 index, exercise stress and muscular testing were assessed at the beginning and after 16 weeks of training program. Exercise training increased significantly HDL-C (17.2%; P < 0.001) and decreased triglycerides (18.9%), HbA_1c (15.0%), fasting plasma glucose (5.4%), insulin resistance (HOMA2 25.2%) and resting blood pressure (P < 0.01). After 16 weeks of training, exercise time (17.8%) and muscular strength increased significantly (P < 0.001). The results indicated that a combined strength and aerobic training program could induce positive adaptations on lipid profile, glycemic control, insulin resistance, cardiovascular function, and physical fitness in post-menopausal women with type 2 diabetes. An erratum to this article can be found at     

Immunomodulatory effects of voriconazole on monocytes challenged with Aspergillus fumigatus: differential role of Toll-like receptors

Voriconazole (VRC) has activity against Aspergillus fumigatus, the most frequent cause of invasive aspergillosis in immunocompromised patients. The combination of VRC and A. fumigatus hyphae induced a more pronounced profile of expression of genes encoding inflammatory molecules in human monocytes than Aspergillus alone did. Herein, we provide further evidence of the potential mechanism underlying this immunomodulatory effect of VRC on human monocytes in response to A. fumigatus hyphae. A significant additive antifungal effect was shown when VRC was combined with monocytes against A. fumigatus hyphae. Both A. fumigatus hyphae and VRC induced pronounced profiles of mRNA and protein expression of Toll-like receptor 2 (TLR2) as well as tumor necrosis factor alpha (TNF-α) in THP-1 monocytic cells compared to untreated cells. The VRC-induced increase was greater than that induced by hyphae. The combination of VRC and hyphae increased mRNA and protein expression of TLR2 and TNF-α to even higher levels than did either VRC or hyphae alone. In contrast, TLR4 expression, both at the mRNA and protein levels, was not increased by either VRC or hyphae or their combination. In addition, significantly more NF-κB was translocated to the nuclei of THP-1 cells treated with VRC than untreated cells. While VRC induced more NF-κB than hyphae did, treatment with the combination of the two factors induced the greatest NF-κB expression. The pronounced profile of TLR2 signaling, TNF-α expression, and NF-κB activation in the presence of VRC suggests an immunomodulatory effect leading to a more efficient response to A. fumigatus.     

COVID-19 and the cardiovascular system-current knowledge and future perspectives

The current coronavirus disease 2019 (COVID-19) pandemic has had devastating impact on populations around the world. The high mortality rates in patients with COVID-19 has been attributed to the influence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its causative viral agent, on several physiological systems in human body, including the respiratory, cardiovascular, and neurological systems. There is emerging evidence on propensity of this virus to attack cardiovascular system. However, various pathophysiological mechanisms by which SARS-CoV-2 interacts with cardiovascular system and leads to high morbidity and mortality, including cardiovascular complications, are poorly understood. This mini review aims to provide an update on the current knowledge and perspectives on areas of future research.     

Primary tuberculosis of the thyroid gland: report of three cases.

We report on three cases with rapidly increasing thyroid masses who were referred with the provisional diagnosis of thyroid carcinoma. In the two cases, the diagnosis of tuberculosis was established after thyroidectomy, but in the third case diagnosis was made pre-operatively with acid fast bacilli (AFB) staining and culture from fine needle aspiration (FNA) material. Although rare, tuberculosis of the thyroid gland should be included in the differential diagnosis of thyroid masses. FNA, AFB staining and culture of the aspirate are important diagnostic tools in these cases.