Safety of the Oral Triphala Recipe from Acute and Chronic Toxicity Tests in Sprague-Dawley Rats.

BACKGROUND: The Indian Ayurvedic herbal formula Triphala (TPL) is known for its pharmacological properties for immunomodulation, anti-inflammation, antioxidant, and anti-cancer. This study aimed to investigate the acute and chronic toxicities of the Triphala recipe in a rat model. METHODS: To assess the acute toxicities, 5000 mg/kg of TPL was orally administered to Sprague-Dawley rats. For chronic toxicities, different dose levels of TPL at 600, 1200, and 2400 mg/kg/day were given daily for 270 days. General health and behaviors and the body and organ weights of the rats were monitored. At the end of the experiment, blood samples were evaluated for hematology and biochemistry profiles. The evaluation of the internal organs' appurtenance and necropsy was performed to confirm the tissue histopathology. RESULTS: The results showed that there was no sign of acute toxicity in the TPL group with a decrease in sex organ weights. No significant differences in the rats' behaviors, physical health, body, or organ weights were found between the controls and the rats receiving the 270/day of oral Triphala at 600, 1200, and 2400 mg/kg/day. However, some alterations in blood chemistries and hematology, including glucose, BUN, red blood cells, Hb, HCT, and MCV, were observed without abnormalities in histopathology. CONCLUSIONS: It has been demonstrated that the long-term use of TPL in rat models is safe. No toxic effects were found, suggesting possible safety for long-term use in humans.

Ocular surface squamous neoplasia in Northern Thailand: a 16-year review.

PURPOSE: To evaluate clinical characteristics, treatments, and outcomes in patients with ocular surface squamous neoplasia (OSSN) at a tertiary center in Northern Thailand. METHODS: Patients diagnosed with either corneal-conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC) from May 2000 to December 2015, were recruited. The patients' demographics, symptoms, clinical characteristics, cytopathology, treatments, and outcomes were reviewed. RESULTS: Overall 171 eyes from 168 patients, 92 eyes were CIN and 79 eyes were SCC. Males were affected in 65.5%. The mean age was 58.8 ± 16.8 (29-99) years. In most cases (60.3%), the tumors were located at the limbus. The most common clinical characteristic was papilliform appearance (46.2%). Human immunodeficiency virus (HIV) infection was found in 37 (22.0%) patients with a mean age of 40.5 ± 7.7 years. The treatments and outcomes were evaluated in 136 eyes whose main initial treatment was wide excision with adjunctive cryotherapy (47.8%), followed by topical mitomycin C (30.9%). The mean follow-up time after treatment was 20.8 ± 2.2 (3-110) months and the recurrence occurred in 18 eyes (13.2%) during the follow-up period. The mean recurrence-free time (months) for CIN was significantly longer than that of SCC (81.3 ± 10.0 [95%CI 61.5 - 101.1] vs 33.2 ± 4.6 [95%CI 24.0 - 42.3], p = 0.030). SCC was the only significant risk factor that influences the recurrence of the tumors with the adjusted hazard ratio of 5.69 (p = 0.005). CONCLUSION: OSSN in Northern Thailand usually involved a limbal area and presented as a papilliform mass. HIV infection should be suspected in young patients. CIN had better outcomes after treatments than invasive SCC.

Tracheal Capillary Hemangioma Successfully Treated With Combined Bronchoscopic Cryotherapy and Argon-Plasma Coagulation.

We report a 43-year-old female who presented with recurrent non-massive hemoptysis for four months. Chest radiograph was normal. Thoracic computed tomography (CT) scan revealed a 0.8-centimeter intraluminal polypoid mass abutting the middle part of trachea. A fiber-optic bronchoscopy demonstrated a lobulated reddish mass at dorsolateral aspect of the right side of tracheal wall. Cryotherapy to remove the mass and argon plasma coagulation to stop bleeding at the stump was performed. The histological evaluation confirmed the diagnosis of a tracheal lobular capillary hemangioma. There was no recurrence hemoptysis nor the recurrence of tumor during a one-year follow-up.

Antitumor Efficacy of the Herbal Recipe Benja Amarit against Highly Invasive Cholangiocarcinoma by Inducing Apoptosis both In Vitro and In Vivo.

Thailand is the country with highest incidence and prevalence of cholangiocarcinoma (CCA) in the world. Due to the frequently late diagnosis that is associated with this disease, most CCA patients are prescribed chemotherapy as a form of treatment. However, CCA is able to resist the presently available chemotherapy, so to the prognosis of this disease is still very poor. In this study, we investigated the anticancer potential of a Thai herbal recipe, Benja Amarit (BJA) against CCA and the relevant mechanisms of action that are involved. We found that BJA inhibited CCA cell viability in a dose-dependent manner, especially in highly invasive KKU-213 cells. The extract induced mitochondrial- and caspase-dependent apoptosis in CCA cells by regulating the nuclear factor-κB (NF-κB) signaling pathway. BJA also triggered autophagy in CCA cells. Nonetheless, the inhibition of autophagy enhanced BJA-induced CCA cell death via apoptosis. An in vivo xenograft model revealed the growth-inhibiting and death-inducing effects of BJA against CCA by targeting apoptosis. However, general toxicity to blood cells, kidneys and the liver, as well as changes in body weight, did not appear. Our findings suggest that the herbal recipe BJA might be used as a potentially new and effective treatment for cholangiocarcinoma patients.

Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats.

BACKGROUND: Bacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters. METHODS: Acute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy. RESULTS: The acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range. CONCLUSION: A single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.

Toxicity evaluation of standardized extract of Gynostemma pentaphyllum Makino.

ETHNOPHARMACOLOGICAL RELEVANCE: To evaluate the safety of standardized extract of Gynostemma pentaphyllum in rats. MATERIALS AND METHODS: The water extract of Gynostemma pentaphyllum was prepared and standardized, the dry powder yielded 6% gypenosides. In the acute oral toxicity test, the single oral dose of 5000 mg/kg of Gynostemma pentaphyllum extract was given to female Sprague-Dawley rats. In subchronic toxicity test, the oral dose of 1000 mg/kg/day of the extract was given to rats in treatment and satellite groups for 90 days. Satellite groups of both sexes were kept for additional 28 days after 90-day treatment. Control rats received distilled water. RESULTS: Standardized extract of Gynostemma pentaphyllum did not cause death or any toxic signs in rats. The daily administration of the extract for 90 days did not produce lethal or harmful effects. Although certain hematological and blood chemistry values (i.e., neutrophil, monocyte, glucose, and serum alkaline phosphatase levels) were found to be statistically different from the control group, however; these values were within the ranges of normal rats. CONCLUSION: Standardized extract of Gynostemma pentaphyllum did not produce mortality or any abnormality in rats.

Predominant mucosal IL-8 mRNA expression in non-cagA Thais is risk for gastric cancer.

AIM: To study gastric mucosal interleukine-8 (IL-8) mRNA expression, the cytotoxin-associated gene A (cagA) mutation, and serum pepsinogen (PG) I/II ratio related risk in Thai gastric cancer. METHODS: There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination, and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery. Tissue samples were taken by endoscopy with 3 points biopsies. The serum PG I, II, and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody for H. pylori were tested by enzyme-linked immunosorbent assay technique. The histopathology description of gastric cancer and non-cancer with H. pylori detection was defined with modified Sydney Score System. Gastric mucosal tissue H. pylori DNA was extracted and genotyped for cagA mutation. Tissue IL-8 and cyclooxygenase-2 (COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction. From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples, all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples. The multivariate analysis was used for the risk study. Correlation and standardized t-test were done for quantitative data, P value < 0.05 was considered as a statistically significant. RESULTS: There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA. The H. pylori infection prevalence in this study is reported by combined histopathology and H. pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity, respectively. The serum PG I/II ratio in gastric cancer is significantly lower than in the non-cancer group, P = 0.045. The serum PG I/II ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log10 ≥ 2 are significant cut off risk differences between Thai cancer and non-cancer, P = 0.03 and P < 0.001, respectively. There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer, P = 0.026. Serum PG I/II ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ > 100 or log10 > 2 are significantly difference between Thai cancer group when compared to non-cancer group, P = 0.013 and P < 0.001, respectively. In the correlation study, low PG I/II ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases. However, there is a trend, but not significant convert correlation between IL-8 mRNA expression level and low PG I/II ratio in Thai positive H. pylori infection. The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology. CONCLUSION: Predominant gastric mucosal IL-8 mRNA expression level, H. pylori infection, and low PG I/II ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.

Role of impression cytology in diagnosis of ocular surface neoplasia.

PURPOSE: To compare the accuracy of impression cytology in the diagnosis of ocular surface neoplasia with tissue histology. METHODS: We reviewed the histories of patients diagnosed with ocular surface neoplasia at the Chiang Mai University Hospital. All patients underwent both impression cytology and tissue biopsy. We compared the results of both methods. RESULTS: There were 55 patients (33 men and 22 women), with an age range of 12-99 years (mean, 51 years). Twenty patients had lesions in the right eye and 35 had them in the left eye. The most common histologic report was conjunctival-corneal intraepithelial neoplasia (38.2%), followed by squamous cell carcinoma (34.5%), nonneoplastic changes of squamous epithelia (10.9%), squamous papilloma (7.3%), conjunctival nevi (7.3%), and malignant melanoma (1.8%). Compared with histologic findings, the positive and negative predictive accuracy of impression cytology was 97.4% and 52.9%, respectively. For squamous neoplasms, squamous cell carcinoma had the highest correlation with histology. The presence of dysplastic cells suggested malignancy. CONCLUSIONS: This study shows that impression cytology might have a promising role in diagnosing ocular surface neoplasia for its high positive predictive accuracy compared with tissue histology. However, a fair negative predictive accuracy indicates that impression cytology is a valuable screening technique, but it is not a "gold standard."

Helicobacter pylori cagA, vacA and iceA genotypes in northern Thai patients with gastric disease.

Helicobacterpylori, a common infectious bacterium, has been linked to chronic gastritis, peptic ulcer and gastric cancer. Gastric biopsy specimens were obtained from 58 northern Thai patients with gastritis, 28 with gastric ulcer, 45 with duodenal ulcer and 4 with gastric cancer. cagA, vacA s1 and iceA gene was found in 88, 98, and 89% of the specimens, respectively. For vacA, the frequency of subtype s1a, s1c and combined sla and s1c was 40, 16, and 41%, respectively. The frequency of subtype s1a/m1 and s1a/s1c/m1 was 27 and 20%, respectively. Fifty-three patients (39%) were infected with multiple vacA genotypes but there was no association with clinical outcome. cagA positive and mixed vacA s1a and s1c strains were found in significantly more cases of duodenal ulcer than gastritis (p < 0.05). For iceA, subtype iceA1 reached a frequency of 60%, whereas subtype iceA2 was only 24%.

Juvenile polyp in Thai children--clinical and colonoscopic presentation.

BACKGROUND: The aim of this prospective study was to describe the clinical characteristics of colorectal polyp in Thai children. METHODS: From December 2002 to February 2005, children under 15 years of age presenting with rectal bleeding were prospectively enrolled. Demographic, clinical, and laboratory information was recorded. Location, number, characteristics, and histopathology of the polyps were noted. RESULTS: There were 32 patients with a mean age of 6.5 years. The most common presenting symptom was hematochezia, followed by prolapsing rectal mass and diarrhea. In 20 patients there was a single polyp, 6 had 2-4 polyps, and 6 were diagnosed with polyposis coli. Most of the polyps were located exclusively at the rectum and sigmoid colon. In only 7 cases were the polyps proximal to the rectosigmoid region. This included 6 patients who had polyps beyond the splenic flexure. All were juvenile polyps without evidence of adenomatous changes. Compared to those with isolated polyps, the patients with polyposis coli had a statistically significant incidence of right-sided polyps (P <0.001) and a history of prolapse of the rectal mass (P = 0.006). CONCLUSIONS: Because of the high prevalence of right-sided polyps and the concern about malignant transformation, colonoscopy should be considered as the initial evaluation in children with rectal bleeding.

Expression of cyclooxygenase-1 and -2 and clinicopathologic features of colorectal cancer in northern Thailand.

Two isoforms of cyclooxygenase, COX-1 and COX-2, have been identified and shown to be involved in tumorigenesis. Although, overexpression of COX-2 in human cancers has been repeatedly reported, no data have hitherto been available for Thai patients. To cast light on the role(s) of COX enzymes in the development and progression of colorectal cancers and to determine the incidence of COX-2 overexpression, the expression levels of COX-1 and COX-2 proteins using Western blot analysis in tumor tissues and adjacent normal tissues obtained from 44 Thai patients with colorectal cancer. Compared with paired normal tissues, COX-2 was overexpressed in 13 of 44 colorectal tumor tissues (29.5%). Overall, COX-2 levels in colorectal tumor specimens were significantly correlated with histological differentiation, in particular in the tumors with poor differentiation (p<0.05). In addition, overexpression of COX-2 was found more frequently in colorectal tumors with lymphatic invasion, regional lymph node metastasis and larger size, although without statistical significance. In contrast to the relatively consistent alteration in COX-2 expression, the level of COX-1 expression was quite varied in tumor tissues. Forty-eight percent of colorectal tumors exhibited a decreased level of COX-1 in comparison to normal tissues and overexpressed in 23%. Thus both isoforms may both play roles in promoting tumorigenesis. However, there was no significant relationship between the alteration of COX-1 protein levels and any pathological features of tumors.

Entomophthoromycosis in Maharaj Nakorn Chiang Mai Hospital.

OBJECTIVE: To review documented entomophthoromycosis patients at Maharaj Nakorn Chiang Mai Hospital from 1985 to 2001. MATERIAL AND METHOD: A retrospective review was performed at Maharaj Nakorn Chiang Mai Hospital from 1985 to 2001. Eight cases of entomophthoromycosis were found between 1988 and 1993, with five patients diagnosed as subcutaneous zygomycosis, I GI entomophthoromycosis and 2 rhinofacial zygomycosis. RESULTS: The subcutaneous zygomycosis group was composed of 5 female patients, aged 7- 77 years. They presented with a painless subcutaneous mass, which was solitary or multiple and most commonly found on the extremities. The duration of disease was between 3 months to 5 years. The cultures grew Basidiobolus ranarum. A case of GI entomophthoromycosis was seen in a 34 year old man, who presented with dyspepsia, multiple intraabodminal masses and peritonitis. Two cases of conidiobolomycosis (rhinofacial zygomycosis) were seen. These two patients were male, 26 and 39 years old, and they presented with unilateral nasal obstruction from a mass at the inferior turbinate. The cultures grew Conidiobolus coronatus. CONCLUSION: Entomophthoromycosis in the northern part of Thailand is rare. The disease should be differentially diagnosed by a chronic painless tumor. The patients in this review responded very well to the recommended therapy.

Cytomegalovirus-associated manifestations involving the digestive tract in children with human immunodeficiency virus infection.

OBJECTIVE: To study the clinical manifestations of gastrointestinal cytomegalovirus disease in children with human immunodeficiency virus infection. METHODS: Review of clinical records of eight human immunodeficiency virus-infected children and histopathologically confirmed gastrointestinal cytomegalovirus disease from 1995 to 2001. RESULTS: Six of the eight children were younger than 1 year. The most common clinical presentations were fever and chronic diarrhea. Lower gastrointestinal hemorrhage and bowel perforation were noted in four and three patients, respectively. The colon was the most commonly affected site, followed by the small bowel and esophagus. The diagnosis was established by histopathology, obtained during endoscopy and surgery. Mucosal edema, erythema, and ulcer comprised the most common endoscopic findings. Two patients with fever, chronic diarrhea, and lower gastrointestinal bleeding developed remission after being treated with a 14-day course of ganciclovir. CONCLUSION: Gastrointestinal cytomegalovirus disease can result in serious life-threatening complications, such as bowel perforation and massive gastrointestinal bleeding. Patients with chronic diarrhea and fever of unidentified cause might benefit from gastrointestinal endoscopy for early diagnosis and treatment. Although ganciclovir does not eradicate the infection and relapses are frequent, this treatment can prevent complications and reduce morbidity.

The endoscopic diagnosis of intestinal capillariasis in a child: a case report.

A 13-year-old boy was diagnosed as having intestinal capillariasis by gastroduodenoscopy. He presented with a 10-month history of chronic abdominal pain and diarrhea. The boy had stayed in central Thailand and had eaten uncooked fish and raw shellfish. Gastroduodenoscopy showed normal jejunal mucosa although histology revealed flattened villi, crypt proliferation, acute inflammation, and eosinophilic granulomata. An egg of Capillaria philippinensis was also seen. The child was treated with mebendazole for 30 days. He had gained six kilograms by the time of his last follow-up.