Lidocaine is an amide-class local anesthetic used clinically to inhibit pain sensations. Systemic administration of lidocaine has antinociceptive, antiarrhythmic, anti-inflammatory, and antithrombotic effects. Lidocaine exerts these effects under both acute and chronic pain conditions and acute respiratory distress syndrome through mechanisms that can be independent of its primary mechanism of action, sodium channel inhibition. Here we review the pathophysiological underpinnings of lidocaine's role as an anti-nociceptive, anti-inflammatory mediated by toll-like receptor (TLR) and nuclear factor kappa-β (NF-kβ) signalling pathways and downstream cytokine effectors high mobility group box 1 (HMGB1) and tumour necrosis factor-α (TNF-α).

An intervention study was implemented on five Indonesian islands highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all eligible persons. The cohort consisted of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P = 0.031). No difference was found between the contact and the control groups (P = 0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearance of infection needs to be determined.

We measured beta-carbolinium cations (BC^plus s), endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP^plus), in the lumbar CSF of 22 patients with idiopathic Parkinson9s disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC^plus s, 2,9-dimethylnorharmanium cation (2,9-Me₂ NH^plus), the most potent neurotoxicant that mirrors MPP^plus in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC^plus s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC^plus content, sum of 2-MeBC^plus and 2,9-Me₂ NH^plus levels, was significantly higher in PD patients than in controls. The 2-MeBC^plus contents significantly increased with the progression of the PD, but 2,9-ME₂ NH^plus decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that ``bioactivated99 BC^plus s, especially 2,9-Me₂ NH^plus s, may be the endogenous causative factors underlying PD. NEUROLOGY 1995;45: 2240-2245

A nested polymerase chain reaction (PCR) specific for Salmonella enterica serovar Typhi was used for the detection of the pathogen in blood, urine, and stool samples from 131 patients with clinical suspicion of typhoid fever. The sensitivity of blood culture, the PCRs with blood, urine, and feces, and the Widal test were 61.8%, 84.5%, 69.3%, 46.9%, and 39.0%, respectively. The sensitivity of the PCRs with blood (P < 0.001) and urine (P = 0.01) were significantly higher, and the sensitivity of the PCR with feces (P > 0.05) was similar to that of blood culture. Combined, the PCRs on urine and feces showed positive results for 16 (70%) of 23 typhoid patients with negative results with blood culture and PCR with blood. These results show that the PCR with blood is a sensitive method for the diagnosis of typhoid fever, and that the PCRs with urine and feces could be useful complementary tests.

Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms. The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of “HMGB1”, “HIF-1 α”, “VEGF”, “DOX” and “Cardiovascular disease” and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article. Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention. HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.