Role of nitric oxide and prostaglandin systems in lithium modulation of acetylcholine vasodilation

The mechanism of lithium action, an effective treatment for bipolar disease, is still unknown. The present study examined the role of nitric oxide (NO) and prostaglandin systems in lithium modulation of acetylcholine in mesenteric vascular bed of rats by cannulating superior mesenteric artery. Acetylcholine (ACh) or sodium nitroprusside was injected under constant controlled flow induced by phenylephrine; therefore, changes in perfusion pressure reflect changes in resistance. Although 0.5 mM or 1 mM lithium-pretreatment of vascular bed causes reduction in ACh-response, 1.5 mM lithium induced no changes and 2 and 2.5 mM lithium potentiated ACh-induced mesenteric vascular bed relaxation compared to control group. Pretreatment of vascular bed with L-NAME or indomethacin decreased ACh-induced relaxation in 2 concentrations of 0.5 and 2 mM of lithium. The vasorelaxation response to sodium nitroprusside, the NO donor, was not different among lithium groups (0.5 and 2 mM) and controls. In conclusion, there is a dual modulation of endothelium-dependent relaxation, including an inhibitory effect at lower dose and a stimulating effect at higher dose of lithium in rat mesenteric vascular bed. NO synthesis or cyclooxygenase inhibition decreased vasorelaxation in both lower and higher doses of lithium, suggesting a role for NO and prostaglandin in this effect.     

Molecular Basis of Autosomal Recessive Chronic Granulomatous Disease in Iran

Introduction  

Chronic granulomatous disease (CGD) is a rare inherited condition resulting from mutations in the genes that encode the proteins of the NADPH oxidase enzyme in phagocytes, rendering these cells incapable of killing invading pathogens.     

Review on the Oncology Practice in the Midst of COVID-19 Crisis: The Challenges and Solutions

As of late 2019, the outbreak of novel coronavirus disease (COVID-19) –that started in China– has rapidly afflicted all over the world. The COVID-19 pandemic has challenged health-care facilities to provide optimal care. In this context, cancer care requires special attention because of its peculiar status by including patients who are commonly immunocompromised and treatments that are often highly toxic. In this review article, we have classified the main impacts of the COVID-19 pandemic on oncology practices –followed by their solutions– into ten categories, including impacts on (1) health care providers, (2) medical equipment, (3) access to medications, (4) treatment approaches, (5) patients’ referral, (6) patients’ accommodation, (7) patients’ psychological health, (8) cancer research, (9) tumor board meetings, and (10) economic income of cancer centers. The effective identification and management of all these challenges will improve the standards of cancer care over the viral pandemic and can be a practical paradigm for possible future crises.     

Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects

TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis.     

Resection of abdominal solid organs using high-intensity focused ultrasound

Our objective was to evaluate high-intensity focused ultrasound (HIFU) for minimizing blood loss during surgery by hemodynamically isolating large portions of solid organs before their resection. A high-power HIFU device (in situ intensity of 9000 W/cm(2), frequency of 3.3 MHz) was used to produce a wall of cautery for sealing of blood vessels along the resection line in surgically exposed solid organs (liver lobes, spleen and kidneys) of eight adult pigs. Following HIFU application, the distal portion of the organ was excised using a scalpel. If any blood vessels were still bleeding, additional HIFU application was used to stop the bleeding. The resection was achieved in 6.0 +/- 1.5 min (liver), 3.6 +/- 1.1 min (spleen) and 2.8 +/- 0.6 min (kidneys) of HIFU treatment time, with no occurrence of bleeding for up to 4 h (until sacrifice). The coagulated region at the resection line had average width of 3 cm and extended through the whole thickness of the organ (up to 4 cm). Blood vessels of up to 1 cm in size were occluded. This method holds promise for future clinical applications in resection of solid tumors and hemorrhage control from high-grade organ injuries.     

Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock

We explored the effects of the nucleoside transport inhibitor draflazine on regional blood flow, O2 extraction capabilities, and tumor necrosis factor (TNF) release in acute endotoxic shock. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin and were divided into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before endotoxin, and 7 dogs served as a control group. Draflazine decreased arterial pressure without influencing cardiac index. Mesenteric and portal blood flow and ileum mucosal perfusion increased, but renal blood flow dramatically decreased. After endotoxemia, the draflazine-treated dogs had a lesser fall in cardiac index, filling pressures, and left ventricular stroke work index, and a lesser increase in pulmonary vascular resistance. After fluid resuscitation, they had a consistently lower renal blood flow and ileum mucosal perfusion, but a higher mixed venous and hepatic oxygen saturation and arterial pH than the control group. When cardiac index was reduced by tamponade to study the O2 extraction capabilities, renal blood flow and ileum mucosal perfusion remained lower in the draflazine group. Draflazine did not influence whole-body O2 extraction capabilities, but it delayed the occurrence of liver O2 supply dependency as indicated by a significantly lower liver DO2crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8 mL/min) and a higher O2ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls (both P< 0.05). On the other hand, draflazine increased intestinal DO2crit (42.4 +/- 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TNF levels remained higher in the draflazine group than in the control group, particularly 3 and 4 h after endotoxin administration. We conclude that nucleoside transport inhibition with draflazine does not alter global and hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow. However, this intervention can improve liver O2 extraction capabilities in acute endotoxic shock.     

Kaposi’s sarcoma following living donor kidney transplantation: review of 7,939 recipients

Introduction  Kaposi’s sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. Methods  Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. Results  Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1–180) months. KS occurred more often in older age when compared to patients without KS (49 ± 12 vs. 38 ± 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). Conclusion  The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.     

Triple-stimulation technique in multifocal neuropathy with conduction block

In patients with multifocal neuropathy with conduction block (CB), CBs located between the root and Erb's point are not detected in nerve conduction studies. We therefore examined whether the triple-stimulation technique (TST) might provide a useful means of detecting CB proximal to Erb's point. Clinical assessments, extensive nerve conduction studies (NCS), conventional transcranial magnetic stimulation, and TST were performed on 10 patients with multifocal motor neuropathy with CB (MMNCB) and 6 patients with Lewis-Sumner syndrome. Conduction blocks located proximal to Erb's point were detected in 9 patients. Of the CBs, 58% were associated with muscle weakness. The use of TST to detect proximal CB improved the sensitivity of the American Association of Neuromuscular and Electrodiagnostic Medicine criteria for definite or probable MMNCB from 60% to 90%. Thus, the TST is a useful means for detection of proximal CB and gives NCS considerable additional diagnostic power.