Study Shorts 4 * NO – Cellular Respiration * Chamomile – NO * Taurine – MELAS * Aspirin – Thromboembolism * Skin Bacteria – Cancer *

Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase

Nitric oxide inhibits cellular respiration, “one of the key ways a cell releases chemical energy to fuel cellular activity”, by competing with oxygen. This may be one of the main reasons the nitric oxide can have detrimental effects. 

“Nitric oxide (NO) reversibly inhibits mitochondrial respiration by competing with oxygen at cytochrome oxidase. Concentrations of NO measured in a range of biological systems are similar to those shown to inhibit cytochrome oxidase and mitochondrial respiration. Inhibition of NO synthesis results in a stimulation of respiration in a number of systems. It is proposed that NO exerts some of its main physiological and pathological effects on cell functions by inhibiting cytochrome oxidase. Further NO may be a physiological regulator of the affinity of mitochondrial respiration for oxygen, enabling mitochondria to act as sensors of oxygen over the physiological range.”

Chamomile: an anti-inflammatory agent inhibits inducible nitric oxide synthase expression by blocking RelA/p65 activity.

Chamomile blocks the release of inflammatory cytokines and nitric oxide in response to bacterial endotoxin (LPS) in cells.

“Chamomile has long been used in traditional medicine for the treatment of inflammation-related disorders. In this study we investigated the inhibitory effects of chamomile on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, and explored its potential anti-inflammatory mechanisms using RAW 264.7 macrophages. Chamomile treatment inhibited LPS-induced NO production and significantly blocked IL-1β, IL-6 and TNFα-induced NO levels in RAW 264.7 macrophages. Chamomile caused reduction in LPS-induced iNOS mRNA and protein expression. In RAW 264.7 macrophages, LPS-induced DNA binding activity of RelA/p65 was significantly inhibited by chamomile, an effect that was mediated through the inhibition of IKKβ, the upstream kinase regulating NF-κB/Rel activity, and degradation of inhibitory factor-κB. These results demonstrate that chamomile inhibits NO production and iNOS gene expression by inhibiting RelA/p65 activation and supports the utilization of chamomile as an effective anti-inflammatory agent.”

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial

Taurine supplementation is effective in decreasing stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes).

“we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period….
The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001).

Aspirin provides adequate VTE prophylaxis for patients undergoing hip preservation surgery, including periacetabular osteotomy

Aspirin prevents post-surgical thromboembolism (VTE).

There are no clear guidelines regarding optimal venous thromboembolism (VTE) prophylaxis for patients undergoing hip preservation surgery (HPS), in particular pelvic osteotomy, which is considered to be a major orthopaedic procedure. The aim of this study was to determine the efficacy of aspirin for VTE prophylaxis in a large cohort of patients undergoing femoroacetabular osteoplasty (FAO) and periacetabular osteotomy (PAO). …… This study demonstrates that the incidence of VTE following joint preservation procedure is acceptably low. Administration of aspirin to patients undergoing FAO or PAO appears to be adequate in reducing the risk of VTE. Only two patients in this cohort developed VTE following HPS.

A commensal strain of Staphylococcus epidermidis protects against skin neoplasia

Bacteria found on healthy human skin produce an anti-cancer compound (6-HAP). Injection of the compound into rats lowered tumor rates from UV/ultraviolet exposure.

“We report the discovery that strains of Staphylococcus epidermidis produce 6-N-hydroxyaminopurine (6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes….. Intravenous injection of 6-HAP in mice suppressed the growth of B16F10 melanoma without evidence of systemic toxicity. Colonization of mice with an S. epidermidis strain producing 6-HAP reduced the incidence of ultraviolet-induced tumors compared to mice colonized by a control strain that did not produce 6-HAP. S. epidermidis strains producing 6-HAP were found in the metagenome from multiple healthy human subjects, suggesting that the microbiome of some individuals may confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense.”