Effect of Cytomodulin-10 (TGF-beta1 analogue) on wound healing by primary intention in a murine model.

OBJECTIVE: To evaluate the effect of Cytomodulin-10 (CM-10), a transforming growth factor-beta analogue, on wound healing by primary intention. METHOD: Sixty male albino rats of Charles Foster strain (100-150 g) were used. After intraperitoneal anesthesia, a cutaneous incised wound (4 cm) was created on the back of each rat, which was closed by silk stitches and allowed to heal by primary intention. They were equally divided as test and control. CM-10 was applied to the test wounds daily. At the end of 7, 14 and 21 days of wounding, 10 rats from each group were sacrificed and their wounds were compared. Outcome measures were: 1) breaking force of wounds, 2) histological assessment of healing and 3) evaluation of angiogenesis. Statistical significance was assessed by Student's t-test, ANOVA and Bonferroni correction. RESULT: There was a significant increase in the breaking force (P<0.001). Histological examination showed early epithelization, increased collagen deposition and decreased inflammatory cellular infiltrate at 1st week in the test group. The treated wounds also demonstrated earlier remodeling. Angiogenesis score was significantly higher in the test wounds at 1st week (40.6 vs. 30.8; P<0.001), but not in the subsequent weeks. CONCLUSION: Cytomodulin is a strong promoter of wound healing by primary intention. It increases tensile strength and induces early epithelization. It also promotes increased collagen deposition, early remodeling and increased angiogenesis.

Comparative evaluation of 5-HIAA (5-hydroxy indoleacetic acid) and HVA (homovanillic acid) in infantile hydrocephalus.

BACKGROUND: Infantile hydrocephalus is a common congenital problem. Functional and behavioral disturbances associated with hydrocephalus may be due to altered neurotransmitters in the brain. The role of neurotransmitters has been established in various psychiatric and neurological conditions. Therefore, we decided to study the role of 5-hydroxy indoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF) of hydrocephalic patients as diagnostic and prognostic marker. MATERIALS AND METHODS: Ventricular CSF samples were taken from hydrocephalic patients peroperatively and at days 7 & 30. Control CSF samples were taken from nonhydrocephalic patients operated for other conditions. Samples were analyzed for 5-HIAA and HVA, and results were obtained accordingly. RESULTS: Values of 5-HIAA and HVA showed a highly significant decrease after shunt insertion. No significant difference in values of 5-HIAA and HVA were observed in relation to age and duration of disease. The CSF ventriculo-lumbar gradient for both 5-HIAA and HVA done in six patients was statistically significant only in the noncommunicating group. CONCLUSION: Both the neurotransmitter metabolites 5-HIAA and HVA are found to be significantly high in the hydrocephalus, but 5-HIAA is a more sensitive parameter. These markers levels decrease after shunt insertion. Thus, estimation of these metabolites could be valuable markers for its diagnosis and follow-up.

Serotonin and 5-hydroxy indole acetic acid in infantile hydrocephalus.

The concentration of metabolites of neurohormones in cerebrospinal fluid (CSF) is an index of turnover of substances in brain parenchyma. The raised intracranial pressure in hydrocephalic children may cause alteration in the metabolism of neurohormones. Serotonin and its metabolite 5-HIAA have been studied extensively in CSF of patients with neuropsychiatric diseases. Hence we studied the neurohormones serotonin and its end product 5-hydroxy indole acetic acid (5-HIAA) in CSF of hydrocephalus infants before and after ventriculoperitoneal (VP) shunt. Ventricular CSF samples form 50 hydrocephalic infants were obtained serially at the time of shunt insertion, and then on day 8 and day 30 postoperatively by direct puncture from shunt chamber using 26G needles. Control CSF samples were taken from otherwise healthy children operated under spinal anesthesia. The samples were analyzed for serotonin and 5-HIAA by spectrofluorophotometric method. At the time of shunt insertion, serotonin was significantly decreased (P<0.05) while 5-HIAA was significantly increased (P<0.001) in hydrocephalic infants. On day 8 and day 30 values of serotonin and 5-HIAA approached the baseline values. In patients who developed VP shunt blockade there was again a rise in levels of 5-HIAA. However, no correlation could be established between the levels of serotonin, 5-HIAA and the duration of hydrocephalus and the type of hydrocephalus. Our study shows increased 5-HIAA concentration in CSF indicating increased turnover of serotonin to its metabolite due to pressure changes in hydrocephalus. Long-term follow-up is required to assess if they could be of prognostic significance as regards to long term attainment of brain functions in hydrocephalic children.

An evaluation of toxicity of Taxus baccata Linn. (Talispatra) in experimental animals.

A toxicological study was performed in albino mice and rat with methanolic extract and isolated alkaloid of Taxus baccata Linn. (family: Taxaceae). LD(50) study showed the higher toxic activity in stem (TXA-1,2,3) as compared with leaf (TXB-1,2,3) extract. As the extract were further fractionated into crude alkaloids and purified by chromatography the toxicity of these fractions were found to be in increasing order as follows: methanolic extract (1) < crude alkaloidal fraction (2) < purified alkaloidal fraction (3). The effects of leaf and stem extract of T. baccata were studied on certain biochemical and haematological parameters of mice and rat after 10, 20 and 30 days of exposure. Among the parameters examined, the exposed animal exhibited significant decrease in total leukocyte count (TLC), lymphocytes and cholesterol level (mg/dl), whereas increase was observed in serum transminases (SGOT, SGPT) and alkaline phosphatase (AP) of TXA-1 and TXB-1 treated groups indicating toxic conditions associated due to liver involvement.

Serum adenosine deaminase levels as an index of tumor growth in head and neck malignancy.

This study was conducted on 40 biopsy proved patients of head and neck cancers,85% of patients presented with squamous cell carcinoma in various grades of differentiation. When seruma denosine deaminase activity was compared between controls and cases, significant increase was found in the activities (control 51.54 ±12.09 IU/L and cases 106.87 ±29.75 IU/ L). The duration of illness didn't reflect any statistical significance with the adenosine deminase activity. It was 97.59 ±62.93 IU/L in case where duration of illness was 98 ±30.98 IU/L in patient with more than one year of disease. The lymph node showed stronger correlation with adenosine deaminase activity, its level was 83.41±1.41 IU/L in patients with N(3) The rise in serum adenosine deaminase activity was found to be directly related to the stage I disease. It was 57.80 ±4.60 IU/ L in patient with stage I disease while in patients with stage IV had 135.87 ±18.39 IU/L of activity. According to histological grading, highest level was found in patients having squamous cell carcinoma( 113.41 ±32 IU/L). The activity of adenosine deaminase decreases with radiotherapy and after surgery. This may help in assessing the decrease in tumour mass and improvement in patient’s clinical condition.

Estimation of tissue DNA content in Wilm's tumour.

DNA genome, is affected by malignant processes. Estimation of DNA content was carried out biochemically using Gile's and Myer's technique to assess its prognostic value in 21 cases of Wilm's tumour. The DNA content of tumour tissue and normal adjoining renal tissue was estimated in each case. The DNA content was significantly higher in Wilm's tumour tissue as compared to normal renal tissue (p < 0.05). As the disease advanced, the DNA content of the tumour further increased. The tumours having unfavourable histology had significantly higher DNA content as compared to favourable histology cases (p < 0.001). Similarly, the patients who died because of the disease, had a very high DNA content as compared to those who survived. Further, it was seen that two fold increase in DNA content indicated advanced stage (III & IV), whereas a three fold or more increase indicated grave prognosis as it was usually seen in advanced stage with unfavourable histology and such cases died early. Thus, the DNA content estimation has a prognostic significance in Wilm's tumour.

Effect of latent iron deficiency on 5-hydroxytryptamine metabolism in rat brain.

Eight weeks of latent iron deficiency in weaned rats maintained on an experimental low iron content diet (18-20 mg/kg) did not significantly alter the packed cell volume and hemoglobin concentration; however, the hepatic and brain nonheme iron contents decreased by 66% and 21% (p less than 0.001), respectively. The tryptophan concentration decreased by 31% and 34% in liver and brain, respectively, in rats on experimental diet (p less than 0.01). The brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid contents were reduced by 21% and 23% (p less than 0.01 and p less than 0.02), respectively. However, in the brain, weight, protein, DNA, and the activities of monoamine oxidase, aldehyde dehydrogenase, and liver tryptophan oxygenase were found to remain unaltered. When rehabilitated with a diet containing 390 mg/kg iron, rats previously maintained on the experimental diet for 2 weeks showed partial recovery in tryptophan levels both in liver and brain. However, brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels remained unaltered. The hepatic iron content improved without any change in brain iron content. The latent iron deficiency produced significant alterations in the metabolism of 5-hydroxytryptamine and brain iron content that could not be recovered 2 weeks after the iron rehabilitation.