Clinical Biomarkers for Diagnosis of Damages in Individuals with Long-Term Exposure to X-Rays.

OBJECTIVE: To determine altered manifestation of plasma proteins in X-rays technicians who are regularly exposed to low doses of radiations over a long period during their job. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: District Headquarters Hospital and Mufti Mahmood Memorial Teaching Hospital; from January 2017 to January 2018. METHODOLOGY: The study enrolled 70 individuals consisting of 50 X-ray technicians working 8 to 12 hours/day for five days per week and 20 unexposed healthy controls. The serum protein expression pattern (concentrations of various serum proteins) was evaluated through cellulose acetate electrophoresis and serum antioxidant status was measured through ferric reducing ability of plasma (FRAP) assay. RESULTS: The antioxidant assay showed significantly low trolox-equivalent antioxidant capacity (TEAC) status and FRAP value in X-ray technicians as compared to controls (p<0.001). Analysis of serum protein demonstrated a significantly reduced concentrations of albumin (p<0.001) and elevated level of the Ɣ-globulins (p<0.001), while other globulins fractions like α1 and ß remain unchanged. There was a strong negative correlation (p<0.001) according to Pearson coefficient (r=87%⁽⁻⁾) between albumin and Ɣ-globulins fraction. Whereas, a positive correlation (p<0.001) (r=46%⁽⁺⁾) between alpha 1 globulin and albumin fraction was observed. A correlation between other globulin fractions and albumin was found statistically significant (p<0.001). CONCLUSION: Elevated serum gamma globulins may be a potential protein biomarker for triage and detection of X-radiation induced damages.

Hyaluronidases: A Therapeutic Enzyme.

BACKGROUND: Hyaluronidase is the most important enzyme found in the interstitial matrix, effectively degrading the hyaluronic acid. Hyaluronidases are extensively found in the venom of various animals such as snake, scorpion, spider and others. Up till now five venom hyaluronidases are identified with a defined three-dimensional structure. These enzymes are involved in different biochemical, physiological and pathological conditions like degradation of hyaluronic acid, embryogenesis, transmembrane diffusion of drugs and toxins, inflammatory and allergic response to antigens, healing of wounds, bacterial meningitis, bacteremia and pneumonia. These enzymes are used as an adjuvant therapy in cancer and to expedite the dispersion and absorption of drugs as well as to reduce the tissue edema. and to reduce the progression of metastatic breast cancer as well as used in ophthalmological procedures in combination with local anesthetics, reduction of dermatological aging, regulation of hyaluronan, as a spreading factor and with numerous clinical applications. CONCLUSION: In this review an attempt was made to summarize the physiological, adjuvaent and therapeutic significance of hyaluronidase enzymes from different animal sources.

Potential Application of Venom Proteins in Designing of Medicines for Treating Human Neurodegenerative Disorders.

BACKGROUND: Neurodegenerative disorder are persistently increasing and relentlessly affecting the individuals, families and society as whole. Regrettably these disorders are resistant to the available drugs, the outcomes are only palliative while the side effects of the therapy harm the patient compliance as well as treatment. Drugs from venomous source have been considered as an effective alternative for such types of disorders, particularly neurodegenerative diseases. Due to emerging advancement in the field of proteomics, genomics and molecular biology, characterization and screening of these novel compounds become more assessable. CONCLUSION: In this reverence, the present study reviews the current consideration of the mode of action and the future prediction concerning the use of novel compounds isolated from arthropods and other venomous animals in the treatment of major neurodegenerative diseases such as Parkinson disease, Alzheimer disease, Multiple Sclerosis, Epilepsy and Amyotrophic Lateral Sclerosis.

Simulation Studies and Dynamic Interaction of Venom Peptides with Ion Channels.

BACKGROUND: Arthropods such as scorpion, snake, insects, and spider as well as the marine animals like sea anemone and cone snails are venomous animals producing venoms with a complex mixture of peptide, poly peptides and small proteins. The disulfide rich peptides isolated from these animals are potent substances which specifically and selectively modulate different ion channels. The significant characteristics of these distinctive pharmacologically potent compounds highlights the molecular details of their peptide-ion channels interactions as well as provides the opportunities for the development of novel and natural therapeutic agents to treat various diseases including neurological disorders also. A good deal is going into the understanding of their therapeutic applications by unrevealing their mode of action. CONCLUSION: In this review, an attempt is made to summarizes the molecular behavior of these venom peptides, their pattern of interactions that how molecular simulation studies are used to investigate the dynamic interaction between these peptides and ion channels, structural prediction of peptide channel complex and calculation of binding free energy.

Potential Applications of Venom Peptides as Anti-Thrombotic Agents for Management of Arterial and Deep-Vein Thrombosis.

BACKGROUND: Thrombus is composed of two main substances i.e. red blood cells and aggregated platelets which make a web of inter-connected fibrin proteins. During injury it prevents bleeding, so it is very useful but it can be very dangerous if it is produced in healthy blood vessels and block the blood flow through it. Mural thrombi attaches with the blood vessels but in most cases do not block it completely. Venoms are an incredible source of peptides having amazing bioactivities with varying number of amino acid residues. Anticoagulant venom peptides however inhibit the enzyme taking part in coagulation like factor Xa and thrombin. The anticoagulant potential of venom peptides have also been reported by the degradation of the fibrin or fibrinogen related to serine or metalloproteases. Designing and development of numerous therapeutic agents or lead molecules mostly for cardiovascular diseases have been motivated from toxins/proteins from snake venoms. For example, disintegrins, a large family of platelet aggregation inhibitors found in viperid and crotalid snake venoms were the basis for designing of platelet aggregation inhibitors such as eptifibatide and tirofiban. CONCLUSION: Ancrod isolated from Malayan pit viper venom can cause reduction in level of blood fibrinogen and has been effectively tried in various ischemic conditions, including stroke. In order to search for novel lead molecules, the emphasis should be on isolation and characterization of pharmacologically active snake venoms proteins affecting blood coagulation and platelet aggregation. In this review an attempt has been made to recapitulates and discuss venoms of different animals and arthropod having anticoagulant peptides for their potential use in therapeutics and diagnostics.

Brachdactyly Instigated as a Result of Mutation in GDF5 and NOG Genes in Pakistani Population.

OBJECTIVES: Brachdactyly a genetic disorder associated with the abnormal development of metacarpals, phalanges or both which results in the shortening of hands and feet. Mutations in the contributing genes has been recognized with the majority of the investigated syndromic form of brachdactyly. The current study was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family. METHODS: Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was used for the genomic screening and linkage analysis to observe the mutation in genes. The samples were collected from Luckki Marwat district, KPK, while the research study was conducted in the department of Biochemistry, Quaid-I-Azam University, Islamabad, Pakistan. RESULTS: After survey, family was identified with brachdactyly type A2 and investigated a heterozygous arginine to glutamine exchange in the growth demarcation factor 5 in all the victim persons. Different types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel GDF5 genes mutations were reported with distinct limb malformation and sequencing of coding region revealed that the mildly affected individuals were heterozygous while the harshly affected individuals were homozygous. CONCLUSION: The current study reported the genetic variability and concluded that the Brachdacytyly type A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new subtype of brachydactyly (BDB2) was instigated as a result of novel mutations in NOG. The mutation has been reported for the first time in Pakistani population and especially in Pushtoon ethnic population.

Evaluation of antibiotic resistant bacteria in underground drinking water and transfer of their resistant character to normal flora of the body.

The untreated surface water for drinking and domestic use is an alarming situation to public health especially in prevalence of antibiotics resistant bacteria. This investigation aimed to isolate and identify the antibiotic resistance bacteria in underground water samples in district Dera Ismail Khan, Pakistan. The underground water samples were collected from four different places using hand pumps (Khyber town, riverside, Gomal University and united town). Cultured on nutrient agar media, identified by Gam staining and biochemical tests. There after antibiotic resistance assay were performed by measuring zone of inhibition of different antibiotics by disc diffusion method. Six different bacterial colonies were isolated and identified as Enterobacteriaceae, Serriata specie, Proteues, Pseudomonas, all these bacterial colonies were 33% resistant to chloramphenicol with and 100% resistant to amoxicillin. Some colonies were also considered as resistant, according to the criteria of National Committee for Clinical Records (NCCL) that less than 10mm zone of inhibition are considered as resistant. Subsequently, the chloramphenicol resistance bacteria were analyzed for their ability to transfer resistant gene to sensitive bacteria. In in-vitro method, an isolate M1b (resistant) was found capable to transfer resistance gene to M1a isolate (sensitive) in nutrient rich environment. It was concluded that antibiotics resistance bacteria found in underground water, moreover capable of transferring the antibiotic resistant character to suitable recipient i.e. normal flora of the body or to other pathogens by conjugation.