Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.     

Magnesium and Fluoride Distribution in Human Cementum with Age

Sixty-two human teeth, obtained from subjects aged 11 to 80 years, were used to determine the magnesium and fluoride concentration and distribution with age in human cementum. Transverse sections were prepared from the root region of teeth. Samples, each 30 μm thick, were abraded in sequence from the cementum surface and the cemento-dentine junction by an abrasive micro-sampling technique. Magnesium concentrations were lower in the cementum surface, and increased towards the cemento-dentine junction (CDJ), while fluoride concentrations were higher in cementum surfaces and tended to decrease towards CDJ. Fluoride distribution patterns were similar to that reported earlier while average fluoride concentration increased with age, however, either no change or decreasing tendencies were observed with magnesium. Received: 5 January 1998 / Accepted: 20 July 2000 / Online publication: 2 November 2000     

Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age

Abstract: Objective: To assess the role of ambient air pollutants in type 1 diabetes in children. Design and methods: Prediagnosis exposure to five air pollutants was studied in two subgroups with onset of type 1 diabetes before and after 5 yr of age, and two matched subgroups of healthy children. Zip codes and dates of residence from birth to diagnosis were used to obtain geographic‐ and time‐specific air concentrations of SO₂, NO₂, ozone (O₃), SO₄, and particulate matter < 10 µm in diameter (PM₁₀). Prediagnosis time‐adjusted pollutant exposure levels were created by summing up zip code‐specific pollution data and dividing by months of exposure from birth to diagnosis. Two‐tailed t‐test and logistic regression were used to evaluate relative effects and test data between cases and controls. Results: Prediagnosis average O₃ exposure was significantly higher in children with type 1 diabetes than in healthy controls. Prediagnosis PM₁₀ exposure was significantly higher in children diagnosed before 5 yr of age, when compared with healthy controls. SO₂ exposure was significantly higher in children with later‐onset diabetes compared with those with early‐onset diabetes (EOD). NO₂, SO₂ and SO₄ exposure was significantly lower in children diagnosed after 5 yr of age, when compared with healthy controls. O₃, NO₂, SO₄ and PM₁₀ levels did not significantly differ between the two diabetic subgroups. Conclusion: Increased ozone exposure may be a contributory factor to the increased incidence of type 1 diabetes. PM₁₀ may be a specific contributory factor to the development of type 1 diabetes before 5 yr of age.     

Uncommon procedure in tracheoplasty; thyrotracheal anastomosis and carinoplasty

Both thyrotracheal anastomosis and carinoplasty are relative rare procedure in routine clinic. We reported each 2 cases of thyrotracheal anastomosis and carinoplasty in 51 cases of tracheobronchoplasty. Thyrotracheal anastomosis with partial cricoidectomy was performed in patients with subglottic stenosis for postintubation stenosis and thyroid cancer using suprahyoid release. Each case need re-intubation after surgery. Montage carinoplasty was performed in 2 patients with advanced lung cancer. Right upper lobe was end-to-side anastomosed to trachea in 1 case, and right basal segment was to left main bronchus in another. It was important both diameter in bronchus and mobilization of the residual lung for this procedure.     

Nerve growth factor is associated with islet graft failure following intraportal transplantation

Nerve growth factor (NGF) has recently been recognized as an angiogenic factor with an important regulatory role in pancreatic β-cell function. We previously showed that treatment of pancreatic islets with NGF improved their quality and viability. Revascularization and survival of islets transplanted under the kidney capsule were improved by NGF. However, the usefulness of NGF in intraportal islet transplantation was not previously tested. To resolve this problem, we transplanted syngeneic islets (360 islet equivalents per recipient) cultured with or without NGF into the portal vein of streptozotocin-induced diabetic BALB/c mice. Analysis revealed that 44.4% (4/9) of control and 12.5% (1/8) of NGF-treated mice attained normoglycemia (≤ 200 mg/dL) (p = 0.195). NGF-treated islets led to worse graft function (area under the curve of intraperitoneal glucose tolerance tests (IPGTT) on post-operative day (POD) 30, control; 35,800 ± 3,960 min*mg/dl, NGF-treated; 47,900 ± 3,220 min*mg/dl: *p = 0.0348). NGF treatment of islets was also associated with increased graft failure [the percentage of TdT-mediated dUTP-biotin nick-end labeling (TUNEL)-positive and necrotic transplanted islets on POD 5, control; 23.8% (5/21), NGF-treated; 52.9% (9/17): p = 0.0650] following intraportal islet transplantation. Nonviable (TUNEL-positive and necrotic) islets in both groups expressed vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α). On the other hand, viable (TUNEL-negative and not necrotic) islets in both groups did not express VEGF and HIF-1α. In the present study, pre-transplant NGF treatment was associated with impaired survival and angiogenesis of intraportal islet grafts. The effect of NGF on islet transplantation may significantly vary according to the transplant site.     

A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans

Background

Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo.

Purpose

This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model.

Method

Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28.

Result

Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P = .037) and day 28 (5.4% versus 13.4%, P = .022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P = .028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P = .48).

Conclusion

Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.     

Post-transplant diabetes mellitus in pediatric liver transplantation

Abstract:  To determine the characteristics of pediatric liver transplant recipients who develop GI and/or PTDM, data on children undergoing their first liver transplant from the SPLIT database were analyzed (n = 1611). Recipient and donor characteristics that were evaluated included age at transplant, gender, race, primary disease, hospitalization status at transplant, BMI, recipient and donor CMV status, donor type, donor age, and primary immunosuppression. GI/PTDM was found in 214 individuals (13%) of whom 166 (78%) were diagnosed within 30 days of transplantation (early GI/PTDM). Multivariate analyses suggests that age >5 yr at transplant, hospitalization at transplant, a primary diagnosis other than BA, early steroid use, and tacrolimus use are associated with increased incidence of early GI. Routine monitoring for the development of GI and post-transplant diabetes is indicated in the short- and long-term care of children after liver transplantation.