History of UV Lamps, Types, and Their Applications.

The use of ultraviolet (UV) light, for the treatment of skin conditions, dates back to the early 1900s. It is well known that sunlight can be of therapeutic value, but it can also lead to deleterious effects such as burning and carcinogenesis. Extensive research has expanded our understanding of UV radiation and its effects in human systems and has led to the development of man-made UV sources that are more precise, safer, and more effective for the treatment of wide variety of dermatologic conditions.

Red cell alloimmunisation in regularly transfused beta thalassemia patients in Pakistan.

BACKGROUND: In Pakistan routine blood group typing of thalassemia patients identifies ABO and Rh(D) antigens only. Therefore, other antigen incompatibilities between blood donor and blood recipient may cause alloimmunisation. OBJECTIVE: The aim of this study was to estimate the frequency of alloimmunisation and to evaluate the risk factors associated with its development in beta (ß)-thalassemia patients receiving regular blood transfusions. MATERIALS AND METHODS: In total 162 ß thalassemia patients were included in this study. An extended red cell antigen panel was performed to detect antibodies. Patients received red cell concentrates, which were matched for ABO and Rh(D) antigens. Clinical and laboratory data were collected and analysed to estimate the frequency of alloantibodies and the factors influencing immunisation in patients on regular blood transfusion. RESULTS: The median age of patients was 6·7 (range: 0·5-25) years. A total of 14 (8·6%) patients developed alloantibodies against red cell antigens. The most frequently occurring alloantibodies was anti-E (2·5%), anti-K (1·8%), anti-e (1·2%) and anti-D (0·6%). Five (3·1%) patients developed more than one red blood cell (RBC) alloantibody. Age at first transfusion in alloimmunised patients was 1·22 ± 0·87 years. The frequency of blood transfusion in alloimmunised patients was 23 ± 8·81 days and in those without alloimmunisation was 31·8 ± 16 days (p = 0·02). Logistic regression analysis showed no independent risk factor associated with alloimmunisation. CONCLUSION: The frequency of transfusion was increased in patients who developed alloantibodies. Typing patients and donors to match for Rh and Kell antigens would prevent more than 90% of RBC alloantibodies and reduce the frequency of transfusion in thalassemia patients.

Introduction to diabetes mellitus.

The chronic metabolic disorder diabetes mellitus is a fast-growing global problem with huge social, health, and economic consequences. It is estimated that in 2010 there were globally 285 million people (approximately 6.4% of the adult population) suffering from this disease. This number is estimated to increase to 430 million in the absence of better control or cure. An ageing population and obesity are two main reasons for the increase. Furthermore it has been shown that almost 50% of the putative diabetics are not diagnosed until 10 years after onset of the disease, hence the real prevalence of global diabetes must be astronomically high. This chapter introduces the types of diabetes and diabetic complications such as impairment of immune system, periodontal disease, retinopathy, nephropathy, somatic and autonomic neuropathy, cardiovascular diseases and diabetic foot. Also included are the current management and treatments, and emerging therapies.

5-Fluorouracil in combination with deoxyribonucleosides and deoxyribose as possible therapeutic options for the Coronavirus, COVID-19 infection.

The recent global pandemic created by the Coronavirus SARS-CoV-2, started in Wuhan, China in December 2019, has generated panic, both in term of human death (4-5% of infected patients identified through testing) and the global economy. Human sufferings seem to be continuing, and it is not clear how long this will continue and how much more destruction it is going to cause until complete control is achieved. One of the most disturbing issues is Covid-19 treatment; although a large number of medications, previously used successfully with other viruses (including Chinese herbal medicines and anti-malaria drugs), are under consideration, there remain questions as to whether they can play a satisfactory role for this disease. Global attempts are ongoing to find the drugs for the treatment of this virus but none of the antiviral drugs used for treatment of other human viral infection is working and hence attempts to find new drugs are continuing. Here the author is proposing that 5-Fluorouracil (5-FU) which when used on its own is failing as an antiviral agent due to the removal of this compound by proof reading ability exceptionally found in Coronaviruses. The author here is proposing to test 5-FU in combination with a number of deoxynucleosides on animal models infected with this Covid-19. Should encouraging results ensue, therapies could then be tried on patients.

Identification of new scavengers for hydroxyl radicals and superoxide dismutase by utilising ultraviolet A photoreaction of 8-methoxypsoralen and a variety of mutants of Escherichia coli: implications on certain diseases of DNA repair deficiency.

8-Methoxypsoralen+UVA (ultraviolet light of 320-400 nm) known as PUVA has been in use for a number of years for the treatment of psoriasis and vitiligo. The treatment possibly works on the basis of UVA photoactivated 8-methoxypsoralen binding to DNA forming both single strand and double strand type damage. We have used Escherichia coli as model system in studying PUVA induced DNA damage and repair. It has been known for some time that the photoactivated 8-methoxypsoralen, besides intercalating with DNA, generates at least two reactive oxygen species (ROS): hydroxyl radicals and superoxide anions, and also singlet oxygen. In this study it has been found that, in E. coli, malate dehydrogenase, succinate dehydrogenase and NADH:ubiquinone oxidoreductase can protect cells from PUVA killing presumably by scavenging these ROS. Possible mechanisms have been proposed for these enzymes as cell protectors. Studies also suggest the potential for the use of PUVA in the treatment of a large number of human diseases. This study also finds that, unlike 8-methoxypsoralen, trioxsalen (4,5',8-trimethylpsoralen, another derivative of psoralens) does not generate ROS by UVA photoactivation; and hence the mode of action of trioxsalen and PUVA overlaps only in the binding of these molecules to DNA in the presence of UVA.

Molecular biology of Fanconi anaemia--an old problem, a new insight.

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a complex mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double-strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation.

Screening of microbes, isolation, genetic manipulation, and physiological optimization of Brevibacterium helvolum to produce and excrete thymidine and deoxyuridine in high concentrations.

Analogues of deoxypyrimidines are used in the treatment of a variety of human ailments. Azidothymidine, or AZT, is one such analogue used to treat AIDS. Thymidine is the precursor of AZT, and its cost contributes to the high price of AZT. Attempts are being made to isolate and genetically manipulate microbes that can produce and excrete this compound in high concentrations. To this end, 145 different microbial species from Zeneca and the American Type Culture Collection were screened. Moreover, soil samples were collected from 36 different sites in England, and microbes from these samples were isolated and screened. >From approximately 25,000 isolates screened as single colonies and from 4,000 in liquid cultures, a strain of Brevibacterium helvolum showed the most promising results. Pyrimidine metabolic pathways of this bacterium were worked out, the isolate was genetically manipulated, and physiological conditions were optimized to increase the production of thymidine and deoxyuridine. These mutants of B. helvolum are considered to be of commercial importance.