Expression of cannabinoid receptors and neurotrophins in human gliomas

Recent studies have shown an anti-tumour activity of cannabinoid receptors CB1 and CB2 in gliomas. This effect was mediated by neurotrophins in breast and prostate carcinoma, while in gliomas this relationship has not yet been considered. The aim of this study was to investigate the expression of cannabinoid receptors CB1 and CB2, neurotrophin NGF and NT-3 and their receptors TrkA and TrkC in glioma and endothelial cells. The analysis was performed in 14 gliomas and 2 non-tumour brain specimens by immunohistochemistry and real-time quantitative-polymerase chain reaction (RTQ-PCR). Gliomas showed a weak immunoreactivity for CB1 and CB2 in tumour and in endothelial cells, and for NGF/TrkA mainly in tumour cells, while a moderate/diffuse immunoreactivity was found for NT-3/TrkC. CB2 was expressed on 3 out of 6 low-grade gliomas and in all high-grade gliomas. Non-tumour brain tissues were weakly positive in astrocytes and endothelium for CB1, CB2, NT-3 and TrkC and negative for NGF and TrkA. By RTQ-PCR, gliomas showed low mRNA levels of NGF/TrkA and moderate levels of CB1, NT-3 and TrkC. CB2 mRNA expression was low or absent. A potential role of cannabinoids, particularly of CB2 agonists devoid of psychotropic side effects, in glioma therapy could have a basis in glioblastomas, because they were all positive, though weakly, to CB2. The presence of neurotrophins and their receptors, mainly NT-3 and TrkC, suggests a possible role of these pathways in glioma growth/invasion, but further investigations are required to verify this hypothesis and a potential relationship between cannabinoids and neurotrophins.     

Opposite effects of internal globus pallidus stimulation on pallidal neurones activity.

Besides clinical efficacy, the mechanisms of action of deep brain stimulation (DBS) are still debated. To shed light on this complex issue, we have taken the opportunity to record the response of globus pallidus internus (GPi) neurones to 100 Hz stimulations in a case of Lesch-Nyhan syndrome (LNS) where four pallidal electrodes were implanted. Three types of response were observed, 2/19 neurones were unaffected by DBS. About 7/19 neurones were inhibited during DBS stimulation and 10/19 neurones were excited during DBS stimulation. Both effects ceased when DBS was turned off. Inhibited neurones were situated lower that exited ones on the trajectory (1.25 and 4.65 mm above the center of GPi respectively). These observations suggest that locally DBS induces a reversible inhibition of neurone firing rate while at the same time distantly exciting the main afferents to and/or efferents from the GPi. Both actions would result in a strong GPi inhibition that does not preclude increased outflow from the GPi.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico

Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.     

Direct demonstration of three different states of the pancreatic cholecystokinin receptor.

We used rat pancreatic acini as well as COS-7cells transfected with the cloned pancreatic cholecystokinin (CCK) receptor andmeasured the abilities of CCK octapeptide (CCK-8) and L-364,718 (a CCK receptorantagonist) to inhibit binding of 125I-labeled CCK-8 (125I-CCK-8) and[3H]L-364,718. With pancreatic acini 125I-CCK-8 bound to two different states ofthe CCK receptor. The high-affinity state (1% of the receptors) had a Kd forCCK-8 of 985 pM and the low-affinity state (19% of the receptors) had a Kd forCCK-8 of 30 nM. [3H]L-364,718 bound to low-affinity receptors and to apreviously unrecognized very-low-affinity state (80% of the receptors) having aKd for CCK-8 of 13 microM. L-364,718 had the same affinity (Kd 3 nM) for each ofthe three different states of the CCK receptor. Similar measurements usingtransfected COS cells also identified three different states of the CCKreceptor, with the very-low-affinity state being the most abundant. Thus, theability of the CCK receptor to exist in three different states is an intrinsicproperty of the CCK receptor molecule itself.     

First metatarsophalangeal arthrodesis: a clinical,pedobarographic and gait analysis study

This study investigated the results of first metatarsophalangeal (MTP) arthrodesis in terms of clinical outcome measures, plantar pressure distribution, and gait patterns. Ten feet in nine patients with severe hallux rigidus (HR) who underwent first MTP arthrodesis were studied. The preoperative evaluation included a subjective questionnaire, physical exam, AOFAS hallux score, radiographs and dynamic pedobarography (EMED). At follow-up (average 34 months) these were repeated, and gait analysis studies were obtained. Patients showed significant clinical improvement based on the subjective criteria. The mean AOFAS score improved from 38 preoperatively to 90 postoperatively. Postoperative EMED analysis showed restoration of the weightbearing function of the first ray, with greater maximum force carried by the distal hallux at toe-off. Kinematic and kinetic gait analysis from each patient's operative limb were compared to the unaffected contralateral limb and to age- and sex-matched healthy subjects. The kinematic data indicated a significantly shorter step length with some loss in ankle plantar flexion at toe-off on the fused side. The kinetic data indicated a reduction in both ankle torque and ankle power at push-off. Clinical results indicated effective pain relief and a high level of patient satisfaction, consistent with previous reports in patients with symptomatic Hallux Rigidus.