Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice

Background and purpose:

Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy.

Experimental approach:

Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB₁, CB₂ and TRPV1 receptor agonist); HU308 (CB₂ receptor agonist), SR141716A (CB₁ receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB₂ receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively.

Results:

Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin.

Conclusions:

Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value.     

Cervical human papillomavirus prevalence and genotype distribution among hybrid capture 2 positive women 15 to 64 years of age in the Gurage zone,rural Ethiopia

Background

Human papillomavirus (HPV) infection is a prerequisite of cervical cancer, the leading cause of cancer mortality in Ethiopian women today. Data on Ethiopian cervical HPV prevalence and genotype distribution are rare, but essential as pre-vaccine baseline data to monitor changes after initiating HPV vaccination. The objectives of this study were to assess the cervical HPV prevalence, genotype distribution and associated correlates among female hospital outpatients in rural Ethiopia.

Methods

We examined a consecutive sample of 537 women 15–64 years of age in rural Ethiopia between November and December 2006. Screening for low risk (LR) and high-risk (HR) cervical HPV infection was performed and HR positive samples were genotyped with a GP5+/6?+?? and SPF10-primer based system.

Results

The age-standardized prevalence of HPV, HPV HR and HPV LR infection was 17.3% (95% CI 14.1-20.5), 15.8% (95% CI 12.7-18.9) and 3.9% (95% CI 2.3-5.6), respectively. Among HC2 HPV HR positive infections (n?=?86), the most common genotype was HPV 16 (24.4%), followed by 52 (11.6%), 56 (10.5%) and 31 (10.5%). Non-married relationship and widowhood, increasing number of lifetime sexual partners, human immunodeficiency virus infection and non-traditional housing type, but not age, were significantly associated with HR HPV infection.

Conclusions

These results on cervical HPV prevalence and genotype distribution may serve as baseline data in evaluating the impact of future HPV vaccination programmes in rural Ethiopia.

     

PROSTANOID ACTION ON THE HUMAN PULMONARY VASCULAR SYSTEM

1. Four types of prostanoid receptor are present on pulmonary arterial vessels of man. Thromboxane (TP) receptors mediate constriction and are blocked by antagonists such as BAY u-3405, GR 32191 and EP169. Prostaglandin (PG) EP₃ receptors also mediate constriction, the agonist potency ranking being SC 46275 > sulprostone > misoprostol≥PGE₂; this action needs to be borne in mind when PGE analogues are used therapeutically. 2. Prostaglandi. E₂ causes relaxation in a few pulmonary artery preparations: an EP₂ receptor may be involved. Prostacyclin, acting through IP receptors, consistently produces relaxation and studies are in progress to determine the contribution made by K⁺-channel opening. Agonist potencies of stable prostacyclin analogues and non-prostanoid prostacyclin mimetics, such as BMY 45778 and the novel diphenylindole CU 23, on human pulmonary artery and platelets are well correlated. Interestingly, the non-prostanoid mimetics show persistent relaxant effects in vitro, which may be related to their high lipophilicities. 3. Prostacyclin and iloprost are being used to treat severe pulmonary hypertension; further study of the pharmacodynamic and pharmacokinetic properties of other IP receptor agonists could produce improve. therapy.     

The prevalence,radiographic appearance,and characteristics of zygomatic air cell defects (ZACDs) in symptomatic temporomandibular joint disorder patients in North Indian population

Purpose

Although the incidence of zygomatic air cell defects (ZACDs) is significantly low in general population, still they pose as a risk factor during surgical procedures like eminectomies and eminoplasties because there is a risk of spread of infection intracranially. Furthermore, such procedures are more common in TMD patients. With this fact in mind, this study was designed to find out the prevalence, radiographic appearance, and characteristics of zygomatic air cell defects in diagnosed symptomatic temporomandibular joint disorder patients.

Method

The study comprised of evaluation of panoramic radiographs of 70 temporomandibular joint disorder (TMD) patients in the age range of 18–30 years selected on the basis of Research Diagnostic Criteria (RDC/TMD). The radiographs were evaluated regarding the presence, variations, and characteristics of ZACDs. Groups were compared by χ ² analysis.

Results

ZACDs were identified in 21 TMD subjects out of 70, giving an overall prevalence of 30 %. Out of 21 ZACDs, nine were in males (42.8 %) and 12 were in females (52.38 %). ZACDs were unilateral in ten TMD patients (47.61 %) and were bilateral in 11 patients (52.38 %).

Conclusion

It can be concluded that the number of ZACDs is surprisingly more in diagnosed TMD patients. This strengthens the need for thorough preoperative imaging evaluation of ZACDs in such patients. Further longitudinal studies are required to find out the long-term effect of ZACDs on symptomatic as well as non-symptomatic TMD subjects. This may prove helpful to appreciate that whether ZACDs have any role in the development TMDs and vice versa. As with many TMD studies, caution should be exercised in interpreting these results until further studies have been carried out on this topic. Ideally, some prospective randomised evaluations with “hard” evidence of the diagnosis with MRI support.     

Therapeutic Modalities for the Prophylactic Management of Postoperative Nausea and Vomiting

The occurrence of postoperative nausea and vomiting (PONV) remains one of the most common complications after general anesthesia. The causes of PONV are multimodal, involving several physiologic pathways that stimulate the vomiting center, including the chemoreceptor trigger zone, the gastrointestinal tract, the vestibular system, the cerebral cortex, and the midbrain. Significant research has been published focusing on the use of different pharmacologic agents and varying anesthetic techniques to prevent and manage PONV. The addition of therapeutic modalities to the arsenal of prophylactic management techniques may decrease patient incidence of PONV by directing treatment to various pathways that stimulate the vomiting center. The purpose of this article is to review briefly the literature and discuss three therapeutic modalities for preventing PONV: perioperative oxygen administration, perioperative intravenous fluid administration, and differing fasting protocols.     

Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse

Fourteen patients with chronic myeloid leukemia (CML) relapsing after allogeneic bone marrow transplant (BMT) were treated with leukocyte transfusions from the original marrow donor (sibling, n = 9; volunteer unrelated, n = 5). The relapse was defined at the molecular level in two cases, cytogenetically in five cases and hematologically in seven cases. Ten patients responded, seven of seven patients with cytogenetic/molecular relapse compared with three of seven with hematologic relapse (P < .03). All five recipients of cells from unrelated donors responded. Eight of the 10 responders have achieved polymerase chain reaction-negative status and this persisted in three patients for more than 2 years; no responder has shown sign of relapse. Reversible marrow aplasia occurred in two patients, both treated in hematologic relapse. Severe graft-versus-host disease occurred in four patients and was fatal in one. We confirm previous reports that donor leukocyte transfusions are effective in the management of CML in relapse after BMT. In this series, therapeutic intervention before the onset of hematologic relapse was associated with an increased likelihood of response and no marrow aplasia.     

Hydroxyurea affects cell morphology, cation transport, and red blood cell adhesion in cultured vascular endothelial cells

Hydroxyurea (HU) significantly increases fetal hemoglobin (Hb) production and concomitantly affects passive erythrocyte K transport and cell volume in patients homozygous for Hb S, thus decreasing disease severity. Red blood cells (RBCs) with Hb S display a greater adherence to vascular endothelial cells (VECs) than do Hb A cells, thus increasing the probability of vaso-occlusive crisis. The effect of HU on the structure and function of VECs is still unknown. In the present study, HU significantly changed, in a dose-dependent manner, the morphology and monovalent cation composition of cultured VECs after incubation in normal culture medium for up to 10 days in the absence and presence of 0.3 (therapeutic dose) and 3.0 (toxic dose) mmol/L HU. Treated cells showed significant morphologic changes such as an increase in apparent cell size and the formation of multinucleated giant cells. The protein content per dish decreased by 50% and 80% at 0.3 and 3.0 mmol/L HU, respectively, accompanied by an increase in cell Na (maximum, approximately 200%) and cell K (maximum, approximately 50%) contents at about days 4 to 6 and 8 to 10, respectively. In addition, HU decreased RBC adherence to VECs in experiments with 51Cr- loaded Hb A or Hb S RBCs. The HU-induced changes in VEC morphology, cation composition, and RBC adherence may be caused or accompanied by alterations in cell membrane permeability, transformation of endothelial cells, or decreased number/density of VEC adhesion molecules. Precise mechanisms of the HU effects warrant further investigation in light of the reported beneficial effects of HU in the treatment of sickle cell anemia.     

Bilateral persistent hyperplastic primary vitreous

We report a case of bilateral persistent hyperplastic primary vitreous (PHPV) in a 5-month-old infant who presented with bilateral leukokoria. The child was referred for occular ultrasound with a clinical suspicion of retinoblastoma. Grey-scale evaluation revealed an echogenic band in the posterior segment of the left globe extending from the posterior surface of the lens capsule to the optic disc. Doppler examination revealed the presence of blood flow in the band. Ultrasound assessment of the contralateral globe showed an elevated mass of echogenic tissue in the posterior segment, in contact with the optic disc. Most cases of PHPV are sporadic and unilateral. Bilateral PHPV is rare. In a study by Pollard of 83 cases, only two patients (2.4%) had bilateral PHPV. The imaging features in this case point toward the diagnosis of bilateral PHPV. We suggest that this entity, although rare, should be considered in the differential diagnosis while evaluating bilateral leukokoria.