Current And Emerging Trends In The Management Of Pyoderma Gangrenosum: A Literature Review.

The first description of Pyoderma gangrenosum (PG) was made about a century ago. It is difficult to understand the aetiology, pathophysiology, and therapy of PG. This disease is believed to be caused by a systemic inflammatory response to neutrophil chemotaxis and faulty innate immune system control. Nearly fifty percent of the cases have underlying systemic symptoms. Significant improvements in PG management have been made over the years. The main goals of treatment are to reduce inflammation and speed up the healing of the PG wound. Even though the most recent medicines show promise, they are found on isolated case reports. The majority of patients are typically managed with topical treatment and local wound care, while resistant cases necessitate immunosuppressive medications. More progress can be made with improvements in technology in deciphering this complex disease and getting a greater understanding of the condition. The present standard therapies for refractory PG are not well supported by studies. In refractory PG, corticosteroids and cyclosporine have historically been administered. Tumour necrosis factor inhibitors are becoming a viable option; nonetheless, this requires careful research and upkeep. This review intended to describe the current trends in managing the PG. Several next-generation treatment options including the conventional therapies introduced to treat PG. We encompass the advantages and disadvantages of new treatments for PG.

Cardiogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells by 5-Azacytidine: A Follow-up In vitro Study.

BACKGROUND: Cell-based therapy is a promising tool in the management of myocardial infarction. AIM OF THE WORK: The aim of this study is to examine the in vitro potential differentiation of murine bone marrow (BM)-derived stem cells into cardiomyocytes using 5-azacytidine after 1, 3, and 5 weeks and follow it up after 8 weeks. MATERIALS AND METHODS: BM-derived mesenchymal stem cells (MSCs) were extracted from the bones of adult albino rats. MSCs were induced with 10 µM 5-azacytidine for 24 h. The cells were examined after 1, 3, 5, and 8 weeks. Cell characterization with immunocytochemistry for detection of CD105, desmin, and T-troponin and transmission electron microscopy was performed. RESULTS: The 5-azacytidine-induced MSCs showed light and electron microscopic histological characteristics resembling cardiomyocytes and progressively expressed the cardiac muscle-specific markers over the 1st, 3rd, and 5th weeks, yet by the 8th week, these parameters were significantly downregulated. CONCLUSION: Prolonged survival of 5-azacytidine-induced MSCs in culture beyond the 8th week resulted in loss of the newly acquired cardiomyocyte characteristics. It is not recommended to prolong the maintenance of 5-azacytidine-induced MSCs in culture on the hope of increasing its cardiogenic potentiality beyond 5 weeks.

Exploring the nature of inclusion bodies by MALDI mass spectrometry using recombinant proinsulin as a model protein.

The present study deals with mass spectrometric investigation to characterize the nature of proinsulin in inclusion bodies. Various derivatives of human proinsulin were cloned, expressed in E. coli and inclusion bodies prepared under weak acidic conditions (pH 6.5), which protected the native thiols. Non-reductive PAGE showed that proinsulin migrated as monomer (approximately 10 kDa). MALDI-MS protocol was developed for the direct analysis of proinsulin derivatives in inclusion bodies. It was found that the masses of the derivatives corresponded to polypeptides containing six cysteines in reduced form. Iodoacetamide or iodoacetic acid treatment of proinsulin inclusion bodies, in suspension under non-reducing conditions and without any chaotropic agents, showed six alkylations, suggesting that these cytoplasmic aggregates were assembled from reduced monomers, with their -SH groups pointing towards hydrophilic surface. The MALDI analysis of inclusion bodies was extended to a proinsulin derivatives labelled with 13C and 15N giving an excellent agreement between experimental and theoretical masses. These mass spectrometric studies also provide early information about post-translational modification as evident in one of the derivatives MTRR-pi showing N-terminal cleavage of methionine. This shows the potential value of the protocol for the accurate analysis of polypeptides, expressed as inclusion bodies, prior to undertaking further purification.

Histological, Immunohistochemical, and Biochemical Study of Experimentally Induced Fatty Liver in Adult Male Albino Rat and the Possible Protective Role of Pomegranate.

Nonalcoholic fatty liver disease is a major health problem and is considered the most common worldwide liver disease. Pomegranate has many biological activities and could modify the risk of hypercholesterolemia. The objective of the current research was to study the histological changes of experimentally induced fatty liver and possible protection by pomegranate. For this purpose, 50 adult male albino rats were divided into four groups, control group, pomegranate treated group that were given pomegranate juice for six weeks, fatty liver induced group that were fed on high fat diet for six weeks and protective group that were fed on high fat diet and received pomegranate juice for six weeks. Histological changes were detected in the fatty liver induced group in the form of disturbed hepatic architecture, dilatation and congestion of central veins, blood sinusoids and portal veins. Most of hepatocytes showed variable degrees of cytoplasmic vacuolation, mitochondrial structural changes, dilatation of endoplasmic reticulum in addition to nuclear structural changes like condensed chromatin, irregular shrunken nuclei and vacuolated nuclei. All these changes were associated with inflammatory cellular infiltrations, deposition of collagen fibers around the central vein, blood sinusoids, portal areas and in between the hepatocytes in addition to significant increase in number of hepatic stellate cells that was proved by electron microscope and confirmed by immunohistochemical study. Moreover, these structural changes were much less pronounced in animals treated with pomegranate either with or before receiving high fat diet. These findings suggested that pomegranate has a protective effect against experimentally induced fatty liver.

The effect of light-activation sources on tooth bleaching.

UNLABELLED: Vital bleaching is one of the most requested cosmetic dental procedures asked by patients who seek a more pleasing smile. This procedure consists of carbamide or hydrogen peroxide gel applications that can be applied in-office or by the patient (at-home/overnight bleaching system). Some in-office treatments utilise whitening light with the objective of speeding up the whitening process. The objective of this article is to review and summarise the current literature with regard to the effect of light-activation sources on in-office tooth bleaching. A literature search was conducted using Medline, accessed via the National Library of Medicine Pub Med from 2003 to 2013 searching for articles relating to effectiveness of light activation sources on in-office tooth bleaching. This study found conflicting evidence on whether light truly improve tooth whitening. Other factors such as, type of stain, initial tooth colour and subject age which can influence tooth bleaching outcome were discussed. CONCLUSIONS: The use of light activator sources with in-office bleaching treatment of vital teeth did not increase the efficacy of bleaching or accelerate the bleaching.

Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production.

Protective effect of Heme oxygenase-1 (HO-1) induction from hypertension was previously reported in a diabetic animal model. Here, the effect of HO-1 induction on vascular complications associated with metabolic syndrome (MetS) was investigated. MetS was induced in rats by fructose drinking for 12weeks while HO-1 was induced by hemin or curcumin administration in the last 6weeks. Then, aortic HO-1 protein expression was assessed, blood pressure (BP) was recorded and serum levels of glucose and insulin were measured. Concentration response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in thoracic aortic cross sections. Aortic reactive oxygen species (ROS) and nitric oxide (NO) generation were also studied. Both hemin and curcumin significantly inhibited the elevated systolic and diastolic BP seen in MetS animals. While not affected by MetS, HO-1 expression was significantly increased by hemin and curcumin treatment. HO-1 induction did not affect the exaggerated vasoconstriction response to KCl and PE. However, HO-1 induction prevented the impaired relaxation and NO generation in aorta isolated from MetS animals. In addition, the HO inhibitor, tin protoporphyrin, abolished the hemin protective effect on relaxation and NO generation. HO-1 induction prevented the elevated hyperinsulinemia associated with MetS. Furthermore, HO-1 induction inhibited ROS production in aorta isolated from MetS animals. In conclusion, Heme oxygenase-1 alleviates vascular complications associated in MetS through maintaining endothelial-dependent relaxation and NO generation in addition to improving insulin sensitivity.

Studies to analyse the relationship between IFNα2b gene dosage and its expression, using a Pichia pastoris-based expression system.

Human interferon α2b (hIFNα2b) is the most important member of the interferon family. Escherichia coli, yeasts, mammalian cell cultures and baculovirus-infected insect cells have been used for expressing recombinant human interferon. Recently a Pichia pastoris-based expression system has emerged as an attractive system for producing functional human recombinant IFNα2b. In this regard, gene dosage is considered an important factor in obtaining the optimum expression of recombinant protein, which may vary from one protein to another. In the present study we have shown the effect of IFNα2b gene dosage on extracellular expression of IFNα2b recombinant protein from P. pastoris. Constructs containing from one to five repeats of IFNα2b-expressing cassettes were created via an in vitro multimerization approach. P. pastoris host strain X-33 was transformed using these expression cassettes. Groups of P. pastoris clones transformed with different copies of the IFNα2b expression cassette were screened for intrachromosomal integration. The IFNα2b expression level of stable transformants was checked. The copy number of integrated IFNα2b was determined by performing qPCR of genomic DNA of recombinant P. patoris clones. It was observed that an increase in copy number generally had a positive effect on the expression level of IFNα2b protein. Regarding the performance of multicopy strains, those obtained from transformation of multicopy vectors showed relatively high expression, compared to those generated using transformation vector having only one copy of IFNα2b. It was also observed that an increase in drug resistance of a clone did not guarantee its high expression, as integration of a marker gene did not always correlate with integration of the gene of interest.

First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients.

Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug.

Late occurrence of lens particle glaucoma due to an occult glass intralenticular foreign body.

We report a case of traumatic mature cataract with a late occurrence of lens particle glaucoma after 11 years of trauma due to a presence of an occult intralenticular glass foreign body which was detected accidentally during the cataract surgery.

Patterns of presentation of malaria in a tertiary care institute in Saudi Arabia.

OBJECTIVE: The occurrence of malaria in a non-endemic area is an exceptional event. Review of clinical experience at the King Faisal Specialist Hospital & Research Centre (a tertiary medical centre located in a non-endemic area) demonstrated a relatively frequent infection rate among patients. We therefore examined circumstances that could contribute to the high rate of occurrence observed. METHODS: We retrieved archived blood smears of patients diagnosed with malaria from the records of the Hematology Section of King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia, followed by a review of the clinical records to extract demographic data, clinical presentations including history of proximate blood transfusion, and travel to, or residence in, areas endemic for malaria. RESULTS: There were 217 patients diagnosed with malaria between 1978 and 1999, (1398 to 1419 Hejira calendar) resulting in an average yearly frequency of 9.86 cases. Males were 2.6 times more frequently affected than females (p<0.001). The majority of patients were infected through natural means, either by residence in endemic areas (N=83) or by travel to one (N=90). A significant minority, 44 (20.3%), became infected through blood transfusion. The majority of blood transfusion-induced malaria occurred in patients who were immunocompromised for various reasons, mostly related to dysfunction of the hematopoietic system or to major surgical insult. The most frequently implicated organism was Plasmodium falciparum, accounting for 74.2% of cases, whilst Plasmodium vivax accounted for 25.4%. CONCLUSION: We demonstrate that patients presenting with malaria are more likely to be males who have been exposed during travel to endemic areas or through blood transfusion. In all cases, Plasmodium falciparum is the most likely organism to be implicated.