Enzymatic and toxinological activities of Hypnale hypnale (hump-nosed pit viper) venom and its fractionation by ion exchange high performance liquid chromatography

Hypnale hypnale (hump-nosed pit viper) has been recently identified as one of the medically important venomous snakes in Sri Lanka and on the southwestern coast of India. The characterization of its venom is essential for understanding the pathophysiology of envenomation and for optimizing its management. In the present study, the biological properties of Hypnale hypnale venom and venom fractions obtained using Resource Q ion exchange chromatography were determined. The venom exhibited toxic activities typical of pit viper venom, comparable to that of its sister taxon, the Malayan pit viper (Calloselasma rhodostoma). Particularly noteworthy were its high activities of thrombin-like enzyme, proteases, phospholipase A2, L-amino acid oxidase and hyaluronidase. The thrombin-like enzyme was mainly acidic and distributed over several chromatography fractions, indicating its existence in multiple isoforms. The hemorrhagic and necrotic activities of the venom were likely associated with the proteolytic enzyme found mainly in the basic fraction. Phospholipase A2 and phosphomonoesterase exist in both acidic and basic isoforms, while L-amino acid oxidase and hyaluronidase are highly acidic. The venom clotting activity on fibrinogens showed distinct species specificity in the following increasing order for clotting time: bovine < rabbit < goat < human < horse < < dog, and was comparable to that of C. rhodostoma venom. Its clot formation on human fibrinogen is gradual and prolonged, a phenomenon suggestive of consumptive coagulopathy as a complication observed clinically. At an intramuscular sublethal dose, the venom did not cause acute kidney injury in a rodent model, contrary to the positive control group treated with Daboia russelii venom. Nephrotoxicity may result from higher venom doses in the context of coagulopathy, as a complication provoked by venom hematoxicity.(AU)

A 7 years retrospective review of skin cancers: A University Malaya medical experience

Background: Skin cancer is ranked the ninth commonest cancer among male and tenth among female in Malaysia. Objective: To determine the pattern of skin cancers and demography of skin cancer sufferers in University Malaya Medical Centre (UMMC). Methods: This is a retrospective review of all histo-pathologically confirmed skin cancers in UMMC from 2004 to 2010. Patients with incomplete or missing data were excluded. Results: A total of 155 patient records were reviewed. The commonest skin cancer was basal cell carcinoma (BCC) (44.5%), followed by squamous cell carcinoma (SCC) (27.1%) and malignant melanoma (MM) (11.6%). The other skin cancers included dermatofibrosarcoma protuberans and cutaneous lymphoma (5.2% each), extramammary Paget’s disease 3.2% and Kaposi sarcoma 2.6%. A majority (78%) of BCC was of nodulo-ulcerative subtype while 50% of MM was of acral lentiginous melanoma subtype. BCC had a significantly higher number of patients from the older age group (>60 years old) compared to other skin cancers (p=0.003). SCC had significantly more male patients than other skin cancers (p=0.006). With the exception of MM, a majority of skin cancers were found on the head and neck. Conclusions: BCC was the commonest skin cancer followed by SCC and MM. Patients with BCC were older with a female preponderance and mainly located on the head and neck. MM was the least common of the three major skin cancers, but has the highest risk of metastasis and mortality.

The trabecular meshwork in acute and chronic angle closure glaucoma.

PURPOSE: To determine the effect of acute and chronic primary angle closure glaucoma (PACG) on the trabecular meshwork. METHODS: Trabecular specimens of 16 consecutive patients with primary angle closure glaucoma (PACG)--6 acute PACG eyes, and 10 chronic PACG eyes without an acute attack--were studied by light and electron microscopy. RESULTS: Acute PACG: The trabecular meshwork revealed a generalised oedema and an accumulation of pigment in the widened trabecular spaces and Schlemm's canal. Attenuated trabecular endothelial cells appeared to be devoid of subcellular components. Chronic PACG: In chronic PACG eyes the trabecular architecture had lost its regular arrangement, with fewer and narrower trabecular spaces and fusion of the trabecular beams in areas. There were numerous electron-dense bodies in the trabecular tissues, both within the trabecular beams and in the extracellular spaces, which had a banded fibrillar structure. An overall loss of endothelial cells was noted; the remaining cells were crowded together and were polymorphic. Melanin pigment was present both within the stroma and in the endothelial cells. CONCLUSIONS: Pigment accumulation in the trabecular spaces and within the cells and a noninflammatory degeneration appeared to be the primary changes in the trabecular meshwork after acute angle closure glaucoma. In chronic PACG eyes, there was evidence of loss of endothelial cells and reactive repair processes. These changes were present in areas away from visible peripheral anterior synechiae. A gonioscopic evaluation of the extent of peripheral anterior synechiae alone may not reflect the extent of trabecular meshwork damage in acute and chronic PACG. Patients experiencing an acute attack of PACG require a long-term follow up, because the intraocular pressure (IOP) may rise later, due to ongoing changes compromising the outflow facility, or due to the effects of aging in the trabecular meshwork.