Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically.

PURPOSE: We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. METHODS: New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70-100 µl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. RESULTS: Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. CONCLUSION: OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics.

Multicentric Castleman's disease in two cases.

Castleman's disease is an atypical lymphoproliferative disorder having two types of presentation--the localized and the multicentric form. The localized form presents as a slowly growing mass with a relatively benign course. Multicentric Castleman's disease has a more aggressive clinical course with diffuse lymph node enlargement and systemic illness. It is rarely seen in childhood and only thirteen cases have been reported in literature. This is the first report of 2 cases from the Indian subcontinent with a maximum follow-up of 44 months one of whom had asplenia.

Efficacy of induction chemotherapy in retinoblastoma, alone or combined with other adjuvant modalities.

BACKGROUND: There are not much data available on the use of newer antimetabolites as an initial treatment modality in retinoblastoma, or their effect on vitreous seedings and de novo foci, especially in the Indian subcontinent. METHODS: To evaluate the efficacy of newer agents as induction chemotherapy, 34 tumors in 22 eyes of 19 children with bilateral retinoblastoma were treated with 2 cycles of carboplatin, etoposide, vincristine, and cyclophosphamide; each cycle was of 1 month duration. The tumor response was evaluated at 2 months and adjuvant salvage modalities (ie, cryotherapy, laser, and/or external beam radiotherapy) were added as needed. The cycles were continued and ophthalmoscopic and ultrasonographic monitorings were performed to determine further tumor response, tumor height regression, effect on vitreous seeds, and other ocular changes. RESULTS: Mean tumor height at presentation was 4.2 mm, which regressed to 2.61 mm at 6 months (P=0.000). The biggest tumor to respond was 12.5 mm, although smaller multiple tumors regressed better. Adjuvant modalities were used in 28 tumor foci in 16 eyes. A follow up of 6 to 24 months (mean, 12.8+/-6.21 months), showed complete regression in 12/34 tumors, partial regression in 15/34, stable disease in 6/34, and 1 tumor progressed despite all therapy. Results in all 6 eyes with vitreous seeds were most gratifying; at 1 year vitreous seeds disappeared in 4 eyes and showed complete calcification in 2. Fresh new lesions were not seen in any eye with complete response after the first 2 cycles of chemotherapy. Recurrences were nil and complications minor. CONCLUSIONS: The overall tumor response (complete and partial) of more than 80% indicates that chemoreduction is an effective modality alone and combined with adjuvant salvage modalities. The results with our treatment regime, even in cases with advanced intraocular retinoblastoma, are encouraging.

Haemorheological factors in the pathophysiology of acute stroke.

Blood viscosity studies were carried out in fourteen patients with acute stroke, eight with cerebral infarction, six with cerebral haemorrhage and in thirteen controls. We observed a statistically significant higher values of plasma, red cell and whole viscosity in patients with acute stroke than in normal controls. Plasma fibrinogen levels were statistically higher (p less than 0.01) in patients than in normal controls. The platelet aggregation was increased in two young adults with acute stroke. The results suggest that the haemorheological factors play an important role in the pathophysiology of stroke patients.

Congenital factor XIII deficiency. A family report.

Four sisters born to consanguineous muslim parents with a bleeding disorder since birth are presented. They also had prolonged umbilical cord bleeding and history of delayed wound healing. Since childhood, they have been developing spontaneous ecchymotic spots. Three out of four sisters had Factor XIII deficiency. Their mother's sisters, who have been developing ecchymotic spots were found to have normal clot stability and Factor XIII levels. Family study indicates autosomal recessive mode of inheritance of the congenital Factor XIII deficiency.

Histopathological changes in skin of children with clinical protein energy malnutrition before and after recovery.

Twenty children with protein energy malnutrition (PEM) exhibiting skin changes, and twenty age- and sex-matched controls were subjected to a skin biopsy under local anaesthesia. Paraffin sections were made and stained with haematoxylin and eosin and also stained for collagen, elastic fibres, mucopolysaccharides, and melanin pigment, and examined. A variable degree of exaggeration of stratum corneum with atrophy of stratum granulosum and prickle cell layers was observed. An appreciable amount of melanin was found in the basal layer in all cases. There was a reduction in the collagen and associated crowding of elastic fibres. The epidermal appendages hair bulbs and hair follicles exhibited atrophy. Sweat glands did not show any changes. After recovery a variable degree of improvement or regression of the changes was observed as compared with the pre-treatment biopsies.