Novel targets and therapies for keloid.

Keloids are the result of aberrant tissue scarring typically occurring in injured skin, and are caused by the overgrowth of granulation tissue or collagen type III during the healing process. There is a genetic component, thus a predisposition can be genetically transmitted. Keloids are difficult to treat because of their postexcisional recurrence, and they have an impact on patient quality of life due to psychological distress caused by cosmetic concerns and functional disability. Treatment ranges from classic corticosteroid therapy to multimodal approaches such as injections, cryotherapy, laser, radiation, radiofrequency ablation and extracorporeal shockwave therapy. Recent discoveries into the pathogenesis of keloid have enabled clinicians to expand the therapeutic options for treatment. The aim of this paper was to review the literature, clarify the general concept of keloid development, and assess emerging treatment options such as stem cell therapy, mitomycin C, bleomycin, interferon, botulinum toxin type A, calcium channel blockers, angiotensin-converting enzyme inhibitors and fat grafting, and the evolutionary advancement towards epigenetic modifications and gene therapy.

Endonasal surgery in the coronavirus era - Birmingham experience.

BACKGROUND: The World Health Organization declared coronavirus disease 2019 a pandemic on 11th March 2020. There is concern regarding performing endonasal surgical procedures because of a high viral load in the nasopharynx. This paper describes our experience in conducting emergency and urgent endonasal operations during the peak of the coronavirus disease 2019 pandemic in the UK. OBJECTIVES: To show the outcome of endonasal surgery during the peak of the coronavirus disease 2019 pandemic and to assess the post-operative rate of nosocomial coronavirus disease 2019 infection. METHODS: A retrospective cohort study was conducted of all patients who underwent high priority endoscopic nasal surgery or anterior skull base surgery between 23rd March and 15th June 2020 at University Hospitals Birmingham NHS Trust. RESULTS: Twenty-four patients underwent endonasal surgery during the study period, 12 were males and 12 were females. There was no coronavirus-related morbidity in any patient. CONCLUSION: This observational study found that it is possible to safely undertake urgent endonasal surgery; the nosocomial risk of coronavirus disease 2019 can be mitigated with appropriate peri-operative precautions.

Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism.

Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-blockers and AII-antagonists it was planned to develop dual α1- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual α1- and AII-antagonists on rat aortic strips for the blockade of known α1- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both α1- as well as AII-receptor antagonists.

Pyrido[1,2-a]pyrimidin-4-ones as antiplasmodial falcipain-2 inhibitors.

Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is a promising target for antimalarial chemotherapy and inhibition of this protease affects the growth of parasite adversely. A series of pyrido[1,2-a]pyrimidin-4-ones were synthesized and evaluated for their in vitro FP-2 inhibitory potential. Compounds (14,17) showed excellent FP-2 inhibition and can serve as lead compounds for further development of potent FP-2 inhibitors as potential antimalarial drugs.

Revelation on the potency of α(1) -blockers - parallel blockade of angiotensin II receptor: a new finding.

CONTEXT: The problem of hypertension has gained enormous proportions in the past decade. Multifactorial etiology and complex pathophysiology of the disease has rendered the treatment of the disease a hard task. Sympathetic nervous system and the renin-angiotensin-aldosterone system are primary contributors of blood pressure homeostasis. OBJECTIVE: Structural similarities were identified among AT(1) and α(1)-antagonists, initiating a speculation that α(1)-antagonists could possibly block the AT(1) receptor and vice-versa. METHODS: To corroborate this speculation, we screened prototypical α(1)-antagonists such as prazosin, doxazosin, and terazosin for antagonism of angiotensin II on rat aortic strips. We also examined the AT(1) antagonists losartan, valsartan, and olmesartan for their possible antagonistic effect, on contractions of rat aortic strips induced by phenylephrine. RESULTS: To our astonishment, we found that prazosin and its analogs which have been reported to have α(1)-antagonistic activity only, were able to shift concentration response curves of angiotensin II. CONCLUSION: Our findings suggest that the potent antihypertensive effect of prazosin-type α(1)-antagonists is not purely due to α(1)-receptor blocking activity of these compounds but also due to blockade of AT(1) receptors. This finding may lead to the development of more potent dual inhibitors which would prove to be of immense value in the control of the scourge of hypertension.

Lipid profile in leukemia and Hodgkin's disease.

A number of epidemiologic studies has been published in recent years showing an increase risk of death from cancer in subjects with low plasma cholesterol levels. Although several authors proposed that hypocholesterolemia is predisposing factor for cancer development, no causative relation has been established so far and that it may be that low plasma cholesterol is secondary to malignant disease. Hence, the present study was undertaken to examine the lipid profile in children patients with leukemia and Hodgkin's disease in comparison with age matched controls. The study included 52 normal healthy controls and 105 patients with leukemia and Hodgkin's disease. Lipid profile included serum cholesterol, HDL & LDL cholesterol and triglycerides. Serum cholesterol, HDL & LDL cholesterol were found to be inversely associated with incidence of cancer, whereas triglycerides were significantly elevated in cancer patients. The inverse association between cancer and serum cholesterol may reflect a physiological response to early undiagnosed stages of cancer.

Clinical significance of lipid profile in cancer patients.

In the present study, we have examined lipid profile in normal healthy age matched control and patients with various malignancies. Analysis of data revealed that total lipids, cholesterol and HDL cholesterol levels are inversely associated with incidence of cancer where as triglycerides levels were significantly elevated in cancer patients. Electrophoretic separation of lipoproteins revealed a significant decrease in the mean values of alpha fraction in patients with malignancy when compared with the corresponding control group. The other fractions beta and pre-beta did not show any change in the mean values in patients with cancer as compared to the normal corresponding control group.