Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Long-term potentiation (LTP) in wide dynamic range (WDR) neurons in the dorsal horn has been suggested to contribute to central sensitization and the development of chronic pain. Indirect experimental evidence indicates an involvement of substance P (SP), in this respect. The aim of the present study was to monitor the extracellular level of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat during and after induction of LTP in WDR neurons in vivo. Electrophysiological recordings of single (WDR) neurons were performed in parallel with microdialysis in the dorsal horn under urethane-anaesthesia. The amount of SP-LI in the microdialysate was determined by radioimmunoassay. As previously shown, high frequency conditioning stimulation of the sciatic nerve induced an increased firing response of WDR neurons. An increased response to C-fibre stimulation, but not A-fibre stimulation, could be determined. A significant increase of the extracellular level of SP-LI in the dorsal horn was detected during, but not after, induction of LTP. These data suggest that SP may be involved in the induction of LTP by high frequency stimulation. However, the maintenance of spinal LTP following high frequency peripheral nerve stimulation does not seem to depend on an increased release of SP.     

Microdialysis in pain research

In vivo microdialysis has been used in preclinical pain research for more than a decade. This valuable tool allows correlations between nociceptive behavior and neurotransmitter release in pain-related CNS sites. However, several methodological issues must be considered to adequately interpret microdialysis data. Thus, the aim of this review is to describe key considerations, potential pitfalls, and important control experiments. We focus on animal experiments which evaluate the effects of noxious stimulation on CNS neurotransmitter release, particularly those that address clinically relevant problems in patients with long-lasting painful conditions.     

Determinants of postoperative morbidity and mortality in children managed for typhoid intestinal perforation in Kano Nigeria

Background

Intestinal perforation is a serious but poorly understood complication of typhoid fever. This study aims to determine the patient factors associated with postoperative morbidity and mortality.

Amplification-free detection of grapevine viruses using an oligonucleotide microarray

A single-colour microarray hybridization system was designed and evaluated for the detection of viruses infecting grapevine. Total RNA (≥0.5μg) from infected plants was converted to cDNA and labelled with Cy3 using two different strategies. While amine-modified and labelled cDNA was adequate for the detection of nepoviruses, the 3DNA technique, a post-hybridization detection method that uses intensely fluorescent dendrimer reagents, was required for the detection of closteroviruses in infected plants. Threshold detection levels were based on the ratio between viral specific and 18S rRNA positive control signal intensities. Oligonucleotides between 27 and 75 nucleotides in length were evaluated and compared. Viruses detected include eight nepoviruses, two vitiviruses, and one each of closterovirus, foveavirus, ampelovirus, maculavirus and sadwavirus. Results of this work demonstrate the potential of microarray technique to detect viral pathogens without sequence bias amplification of template RNA.     

Troglitazone suppresses c-Myc levels in human prostate cancer cells via a PPARγ-independent mechanism

Troglitazone is a ligand for the peroxisome proliferator activated receptor gamma (PPARγ) that decreases growth of human prostate cancer cells in vitro and in vivo. However, the mechanism by which troglitazone reduces prostate cancer cell growth is not fully understood. To understand the signaling pathways involved in troglitazone-induced decreases in prostate cancer growth, we examined the effect of troglitazone on androgen-independent C4-2 human prostate cancer cells. Initial experiments revealed troglitazone inhibited C4-2 cell proliferation by arresting cells in the G(0)/G(1) phase of the cell cycle and inducing apoptosis. Since the proto-oncogene product c-Myc regulates both apoptosis and cell cycle progression, we next examined whether troglitazone altered expression of c-Myc. Troglitazone decreased c-Myc protein levels as well as expression of downstream targets of c-Myc in a dose-dependent manner. In C4-2 cells, troglitazone-induced decreases in c-Myc protein involve proteasome-mediated degradation of c-Myc protein as well as reductions in c-Myc mRNA levels. It appears that troglitazone stimulates degradation of c-Myc by increasing c-Myc phosphorylation, for the level of phosphorylated c-Myc was elevated in prostate cancer cells exposed to troglitazone. While troglitazone dramatically decreased the amount of c-Myc within C4-2 cells, the PPARγ ligands ciglitazone, rosiglitazone and pioglitazone did not reduce c-Myc protein levels. Furthermore the down-regulation of c-Myc by troglitazone was not blocked by the PPARγ antagonist GW9662 and siRNA-mediated decreases in PPARγ protein. Thus, our data suggest that troglitazone reduces c-Myc protein independently of PPARγ.     

Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial

Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized to a protocol using FDC therapy as second and third steps compared with a protocol that used the same medications in free pill combination therapy for these steps. Eligible patients were adults (≥18 years) with hypertension. The primary outcome was the odds of a patient being controlled at their last visit between baseline to 6-month follow-up in the FDC group compared to the free pill group. 4427 patients (mean [SD] age: 49.0 [12.4] years, 70.5% female) were registered with mean (SD) baseline systolic/diastolic blood pressure 155 (20.6)/96 (13.1) mm Hg. Baseline characteristics of groups were similar. After 6-months, hypertension control rate improved in the two treatment protocols, but there were no differences between the groups after adjustment (FDC = 53.9% versus free pill combination = 47.9%, cluster-adjusted p = .29). Adverse events were similarly low (<1%) in both groups. Both protocols improved hypertension control rates at 6-months in comparison to baseline, though no differences were observed between groups. Further work is needed to determine if upfront FDC therapy is more effective and efficient to improve hypertension control rates.     

Approaching COVID-19 with epidemiological genomic surveillance and the sustainability of biodiversity informatics in Africa

COVID-19 is an acute respiratory illness caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). The first case was reported in Africa on February 14, 2020 and has surged to 11 million as of July 2022, with 43% and 30% of cases in Southern and Northern Africa. Current epidemiological data demonstrate heterogeneity in transmission and patient outcomes in Africa. However, the burden of infectious diseases such as malaria creates a significant burden on public health resources that are dedicated to COVID-19 surveillance, testing, and vaccination access. Several control measures, such as the SHEF2 model, encompassed Africa's most effective preventive measure. With the help of international collaborations and partnerships, Africa's pandemic preparedness employs effective risk-management strategies to monitor patients at home and build the financial capacity and human resources needed to combat COVID-19 transmission. However, the lack of safe sanitation and inaccessible drinking water, coupled with the financial consequences of lockdowns, makes it challenging to prevent the transmission and contraction of COVID-19. The overwhelming burden on contact tracers due to an already strained healthcare system will hurt epidemiological tracing and swift counter-measures. With the rise in variants, African countries must adopt genomic surveillance and prioritize funding for biodiversity informatics.