Current concepts on the pathogenesis of the antiphospholipid syndrome

The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (beta2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.     

Intraoperative Radioisotope Injection for Sentinel Lymph Node Biopsy

Background  Preoperative injection of technetium-99 m sulfur colloid (Tc-99) in the Nuclear Medicine Department for localizing sentinel lymph nodes (SLNs) can be extremely painful for the patient. The difficulties in scheduling and the delay in starting surgery can be frustrating for the patient and the surgeon. We hypothesized that intraoperative injection facilitated by the subareolar technique would obviate the problems associated with preoperative injection. Methods  We performed an institutional review board-approved prospective study of patients with operable breast cancer who were candidates for an SLN biopsy from October 2002 to January 2006 at our institution. After induction of general anesthesia, patients underwent a subareolar injection of 1 mCi Tc-99 unfiltered and blue dye. Data comparing preoperative cost were collected. Results  A total of 236 patients had 252 intraoperative SLN procedures. The mean patient age was 57.3 (range, 24-88) years. The mean ± standard deviation time from injection to incision was 25.5 ± 16.2 minutes. Identification rate was 96%, and the number of SLNs identified per patient was 1.6 ± .8. The count of SLN was 60,313 ± 134,692 with 20% SLN positivity. Tumor staging distribution was standard staging terminology for an in situ cancer (Tis) = 17 with 0% (+) SLN, T1 = 115 with 11% (+) SLN, T2 = 56 with 29% (+) SLN, T3 = 19 with 37% (+) SLN, and T4 = 4 with 50% (+) SLN. Maximum exposure to the surgeon was well below maximum, at 100 μSV/mo. Preoperative injection had an additive charge of $1325 associated with it for imaging, injection, and interpretation of images by physician. Conclusion  Intraoperative subareolar injection of Tc-99 localizes the SLN and avoids the pain, vasovagal events, delays, and cost associated with preoperative procedure.     

19F NMR as a powerful technique for the assay of anti-psychotic drug haloperidol in human serum and pharmaceutical formulations

19F nuclear magnetic resonance was used as a suitable analytical tool for the identification and selective determination of haloperidol in human serum and pharmaceutical preparations. The method is based on the integration of appropriate signals of haloperidol and trifluoroacetic acid as an internal standard. The proposed method is a rapid and facile, while without any sample pretreatment, manipulation of large samples and lengthy instrument time. The regression equation for haloperidol in human serum showed a good linearity in the range of 60-600 microg ml(-1) with a detection limit of 1.4 microg ml(-1). The mean recovery results on human serum samples ranged from about 96-103%, with relative standard deviations <8%. The method was also applied successfully to the determination of haloperidol in real pharmaceutical samples, and compared with the results obtained by a reference method. The drug's degradation was studied by the proposed method in hydrochloric acid media and main products were identified.     

Involvement of hypothalamic pituitary adrenal axis on the analgesic cross-tolerance between morphine and nifedipine

Bidirectional cross-tolerance develops between opioids and Ca(2+) channel blockers relating to their antinociceptive effects; however, the role of hypothalamic pituitary adrenal (HPA) axis on this action has not been elucidated yet. We examined the analgesic cross-tolerance between morphine and nifedipine, a dihydropyridine calcium channel blocker, in intact and adrenalectomized (ADX) rats and also evaluated modification of HPA activity during this phenomenon. The tail-flick test was used to assess the nociceptive threshold. The plasma level of corticosterone, as a marker of HPA function, was measured by radioimmunoassay. Our results showed that, in sham operated rats which were chronically treated with morphine, nifedipine failed to affect nociceptive threshold but it could induce significant antinociceptive effect in ADX morphine treated animals. This effect was reversed by corticosterone replacement. Furthermore, morphine could not induce analgesic effect either in sham operated or in ADX animals that received chronic nifedipine. Chronic morphine inhibited the effect of nifedipine on corticosterone secretion but nifedipine treatment had no effect on morphine-induced corticosterone secretion. Based on these results, we can conclude that HPA axis is involved in the induction of cross-tolerance between morphine and nifedipine due to chronic morphine and not nifedipine treatment.     

Short-term ferrous sulfate supplementation in female blood donors

BACKGROUND: Iron deficiency is a public problem in women, which contributes to the high percentage of deferred blood donations in this group. This study evaluated the effect of iron supplementation in improving iron stores to promote safe blood donation in women. STUDY DESIGN AND METHODS: A total of 412 female blood donors were randomly recruited for the study. The volunteers were scheduled for an initial visit and three subsequent visits at 4-month intervals for possible repeat donation. Each volunteer was given 21 tablets of 150 mg of ferrous sulfate or placebo to be taken three times daily for 1 week after each blood donation. Their hemoglobin (Hb) concentration, hematocrit (Hct), serum ferritin, total iron-binding capacity (TIBC), and percent saturation of the TIBC were tested throughout the course of the study. RESULTS: The group taking ferrous sulfate showed no significant difference between the mean initial and final result for any of the values other than Hb values, whereas there was a significant decline in mean Hb, Hct, serum iron, serum ferritin, and percent saturation in the group taking placebo. Hb concentrations declined significantly in both groups; however, it was more severe in the placebo group when compared to the ferrous sulfate group. The relative risk of iron deficiency in placebo group was 3.6 (95% confidence interval = 1.73-7.74). CONCLUSION: The results indicate that supplementation therapy can be considered as one of the strategies to promote safe blood donation in women. A quantity of 150 mg of elemental iron per day as ferrous sulfate, however, is not the correct dose for Iranian female donors.     

An acquired translocation in JAK2 Val617Phe-negative essential thrombocythemia associated with autosomal spread of X-inactivation

The acquired mutation Val617Phe in the tyrosine kinase JAK2 was recently identified in most but not all patients with classical myeloproliferative disorders. We describe a cytogenetic and molecular study of a JAK2Val617Phe-negative case of essential thrombocythemia harboring the acquired translocation t(X;5)(q13;q33). We show that this involves the inactive X-chromosome and is associated with silencing of autosomal genes within the adjacent 5q minus syndrome common deleted region. This is the first documented example of autosomal gene silencing adjacent to an X-autosome breakpoint in human malignancy and such a mechanism may underlie the pathogenesis of related disorders with translocations involving Xq13.     

Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide

Metabolic Brain Disease - Opioid-induced neuroinflammation plays a role in the development of opioid physical dependence. Moreover, nitric oxide (NO) has been implicated in several oxidative and...     

Pretreatment with combined low-level laser therapy and methylene blue improves learning and memory in sleep-deprived mice

Lasers in Medical Science - Low-level laser therapy (LLLT) and methylene blue (MB) were proved to have neuroprotective effects. In this study, we evaluated the preventive effects of LLLT and MB...     

A novel haemostatic powder delivery device applicable in minimally invasive surgery

Haemostatic powder is an effective solution commonly used in various open surgeries. However, there is no specific intra-abdominal delivery device for application of haemostatic powder at the bleeding site during minimally invasive surgery (MIS). In this study, design, construction and test of a novel powder delivery device were carried out. The device uses pressurized gas to deliver the haemostatic powder to the bleeding point. The effect of the gas pressure and the spraying distance on the geometry of the powder dispersion surface area was investigated and found to be significant. The findings indicate that the driving gas pressure range of 60–80?mmHg and the spraying distance range of 2–5?cm achieve the most concentrated powder dispersion surface area. Additionally, in vivo experiments confirmed the effectiveness of the device in live tissue.