Monosodium glutamate altered renal architecture and modulated expression of NMDA-R, eNOS, and nNOS in normotensive and hypertensive rats.

Monosodium glutamate (MSG) administration has been shown to pronounce hypertension and oxidative status with increased renal blood flow (RBF), however, the precise mechanisms of action have never been demonstrated. This study aimed to investigate the MSG action by studying the alteration in renal architecture and specific protein expression in 2-kidney-1-clip hypertensive comparing to sham operative normotensive rats. The administered doses of MSG were 80, 160, or 320 mg/kg BW daily for 8 weeks. Using routine chemical staining, the congestion of glomerular capillaries, a lesser renal corpuscles and glomeruli size, a widen Bowman capsule's space, an increase in mesangial cell proliferation and mesangial matrix, renal interstitial fibrosis, focal cloudy swelling of renal tubular epithelial cells were observed. Immunological study revealed an increase in the expression of N-methyl-D-aspartate receptor (NMDA-R) and endothelial nitric oxide synthase (eNOS) but a decrease in neuronal NOS (nNOS). It is suggested that MSG may upregulate the NMDA-R levels which responsible for the oxidative stress, glomerular injury, and renal interstitial fibrosis. The NMDA-R may also stimulate eNOS overexpression which resulted in renal microvascular dilatation, a raise in RBF and GFR, and natriuresis and diuresis promotion. Long-term exposure of MSG may trigger adaptation of tubuloglomerular feedback through nNOS downregulation.

Garcinia dulcis Extract Alleviates Inflammation in Kidney and Liver of the 2-Kidney-1-Clip Hypertensive rat.

Garcinia dulcis (GD) extract possesses anti-hypertensive property that are poorly characterized. This study aimed to investigate an anti-inflammatory effect of GD flower extract in the 2-kidney-1-clip (2K1C) hypertensive compared to sham operative (SO) rat. Male Wistar rats were divided into 2 groups; the 2K1C group in which a silver clip was placed around renal artery to induce hypertension, and the SO normotensive group. Four weeks later, each group of rats were further divided into 2 subgroups, each subgroup was orally gavaged of either corn oil (vehicle) or 50 mg/kg BW GD extract daily for 4 weeks. The malondialdehyde (MDA) levels in serum, liver, and kidney were determined. Hematoxylin and eosin staining was carried out for histological examination, Periodic acid - Schiff staining for glomerular injury, Masson's trichrome staining for renal fibrosis, and immunohistochemistry for either tumor necrosis factor alpha (TNF-α) or endothelial nitric oxide synthase (eNOS) investigation. Taken together, our results demonstrated that GD flower extract decreased the MDA level in both serum and liver and kidney tissue and suppressed the expression of TNF-α in both liver and kidney of 2K1C hypertensive rats. Mesangial cell proliferation, expansion of mesangial matrix, widening Bowman's capsule space, congestion of glomerular capillary and vessel, cloudy swelling of renal tubular epithelial cell, and renal fibrosis were observed in the kidneys of 2K1C rats. Therefore, we concluded that GD flower extract can alleviate liver and kidney inflammation in which partially attenuates the glomerular injury in the 2K1C rat.

Cardiovascular Protective Effect of Garcinia dulcis Flower Acetone Extract in 2-Kidney-1-Clip Hypertensive Rats.

Morelloflavone and camboginol are bioactive compounds purified from Garcinia dulcis (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was to examine the cardiovascular protective effect of GD flower acetone extract in 2-kidney-1-clip (2K1C) hypertensive rats. Male Wistar rats underwent 2K1C or sham operation (SO) and were housed for 4 weeks. Each group of rats, then, was further divided into 2 subgroups receiving oral administration of either 50 mg/kg BW GD extract or corn oil (vehicle) daily for 4 weeks. Noninvasive blood pressure (BP) and body weight were measured weekly throughout the study. Subsequently, the invasive measurement of arterial BP and the heart rate were determined in all anesthetized rats. The baroreceptor reflex sensitivity (BRS) was investigated by injection of either phenylephrine or sodium nitroprusside for bradycardia or tachycardia response, respectively. Histological examination of the heart and thoracic aorta was also performed in order to investigate the general morphology and the tumor necrosis factor alpha (TNF-α) expression. We found that the GD flower extract significantly diminished the BP and restored the impaired BRS. Moreover, it also decreased the TNF-α expression in the cardiac muscle and thoracic aorta of 2K1C when compared to the SO group. Taken together, our data showed that GD flower extract exhibits the cardiovascular protective effect in the 2K1C hypertensive rats.

The risk of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category subgroups: a Thai institute experience.

INTRODUCTION: This study investigated the rate of reporting and the risk of malignancy (ROM) for atypia of undetermined significance (AUS) subgroups in a Thai population. AUS, which is category III of the Bethesda System for Reporting Thyroid Cytopathology, is a problematic diagnosis for thyroid nodule management because the risks of malignancy are diverse. MATERIALS AND METHODS: Patients who underwent thyroid fine needle aspirations between January 2015 and December 2019 were included in this retrospective study. Gender, age, and nodule features were described, and all slides were re-evaluated and categorized into 2 subgroups: AUS-Nuclear (including cytology atypia and cytologic and architectural atypia) and AUS-Other (including architectural atypia, oncocytic atypia, and atypia not otherwise specified). The lower and upper limits of ROM were calculated for each subgroup. RESULTS: Of total, 258 out of 2995 fine needle aspirations (8.6%) were diagnosed as AUS. The patients were predominantly female (88.9%), with a mean age of 54.1 years. The average nodule size was 2.5 cm. Of the 258 AUS patients, 81 (38.9%) had histological correlations. The ROM for the AUS category was 9.1% to 23.5%. The ROM of the AUS-Nuclear and AUS-Other were 11.1% to 27.3% and 2.2% to 6.7%, respectively. Features of pseudonuclear inclusions had the highest ROM (33.3%-42.9%), followed by pale chromatin (28.57%-47.06%). CONCLUSIONS: Less than ten percent of our interpretations were AUS, which is acceptable in our practice. Cytological atypia harbored the highest ROM. Studies of associations between cytology and histology may aid in improving diagnostic criteria for this population.

Effectiveness of losartan on infrapatellar fat pad/synovial fibrosis and pain behavior in the monoiodoacetate-induced rat model of osteoarthritis pain.

Infrapatellar fat pad (IFP)/ synovial fibrosis is closely associated with the clinical symptoms of joint pain and stiffness, which contribute to locomotor restriction in osteoarthritis (OA) patients. Hence, this study was designed to gain insight on whether losartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has therapeutic benefit to reverse IFP/synovial fibrosis and secondarily to attenuate pain behavior. In male Wistar rats with monoiodoacetic acid (MIA)-induced IFP/synovial fibrosis, a possible role for increased AT1R expression in the pathogenesis of IFP/synovial fibrosis was assessed over an 8-week period. Pain behavior comprised static weight bearing and von Frey paw withdrawal thresholds (PWTs), which were assessed once or twice weekly, respectively. Groups of MIA-rats received oral losartan (30-mg/kg; n = 8 or 100-mg/kg; n = 9) or vehicle (n = 9) for 28-days according to a prevention protocol. Animals were euthanized on day 28 and various tissues (IFP/synovium, cartilage and lumbar dorsal root ganglia (DRGs)) were collected for histological, immunohistochemical and western blot analyses. Administration of once-daily losartan for 28-days dose-dependently attenuated the development of static weight bearing. This was accompanied by reduced IFP/synovial fibrosis and suppression of TGF-ß1 expression. Chronic treatment of MIA-rats with losartan had an anti-fibrotic effect and it attenuated pain behavior in this animal model.

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis.

BACKGROUND: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. METHODS: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. RESULTS: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. CONCLUSION: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.

False-Negative Rate of Papanicolaou Testing: A National Survey from the Thai Society of Cytology.

OBJECTIVE: To evaluate the performance of Papanicolaou smear screening in Thailand at the national level, and to propose recommendations for continuing quality control. STUDY DESIGN: This study was conducted by The Thai Society of Cytology and involved 124 laboratories in 76 provinces during 2010-2014. Random sampling suggested recalling of 10% of slides defined as negative at routine screenings (10% random rescreening [R10] model) directly from the reading unit. RESULTS: Out of 330,075 smears covered by the rescreening project throughout its 5-year duration, the rates of abnormal, unsatisfactory, and normal results were 0.63, 1.82, and 97.55%, respectively. Abnormal findings were largely represented by ASC-US (54%) and L-SIL (21%). The average false-negative rate (FNR) measured at the level of L-SIL and higher was 13.8%. CONCLUSION: The national project was developed to address the accuracy of cervical cancer screening and to promote internal quality assurance based on the R10, on-site surveys, and education. The major output parameters of this study (FNR and number and distribution of abnormal cases on rescreening) improved significantly in the main phase of the project (2012-2014), after revising substantial logistics issues encountered during the first 2 years of this study. This project provided objective measurable evidence related to the quality of cytology-based cervical cancer screening in Thailand.

Co-Existing Ovarian Mucinous Cystadenocarcinoma with Mature Cystic Teratoma: A Rare Case Report.

Background: Mature cystic teratoma is the most common benign germ cell ovarian tumor. Malignant transformation is uncommon. The pathology is mostly composed of squamous cell carcinoma. Mucinous cystadenocarcinoma should be differentiated between malignant transformation and the coincidental occurrence. Case Report: A case of an early stage mucinous ovarian cancer co-existing with mature cystic teratoma at the same ovarian side was reported. A 57-year-old woman presented with incidental palpable pelvic mass for two weeks. Right ovary consisted of multiloculated cyst and mature cystic teratoma. The patient underwent an exploratory laparotomy for a large ovarian cyst evaluation. Mucinous ovarian cancer was diagnosed as FIGO stage IC3 after operation. Histopathology report showed mucinous cystadenocarcinoma and mature cystic teratoma of the right ovary. There was no additional abdominal abnormality. Immunohistochemistry staining supported the diagnosis of metastatic adenocarcinoma of colon or intestinal type of mucinous ovarian cancer. Further investigation for locating other primary cancer site was then performed. The result was negative. The intestinal-type mucinous ovarian cancer co-existing with mature cystic teratoma of the right ovary was the final histopathological reading. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery. The patient showed complete remission at the end of the chemotherapy treatment. Conclusion: This was a rare case of mucinous ovarian cancer co-existing with mature cystic teratoma. Clinical acumen, immunochemistry staining and metastatic survey investigation played important roles for the final diagnosis.

Cytohistologic discrepancy of high-grade squamous intraepithelial lesions in Papanicolaou smears.

OBJECTIVES: To evaluate the frequency of cytohistologic discrepancy of high-grade squamous intraepithelial lesions (HSILs) in Pap smears and associated factors. METHODS: Medical records of 223 women with HSIL Pap smears who were treated at Thammasat University Hospital were reviewed. Data on age, parity, menopausal status, contraceptive use and colposcopic directed biopsy and loop electrosurgical excision procedure (LEEP) pathology results were recorded. RESULTS: Mean (SD) age of patients was 38.0 (9.4) years. The majority were premenopausal (86.5%) and multiparous (83.9%). Cytohistologic discrepancy between the Pap test and colposcopic-directed biopsy histology was 45.7% and that between the Pap test and LEEP histology was 29.5%. Fifty-four (24.2%) women had no high-grade CIN on both colposcopic directed biopsy and LEEP. Nulliparity, postmenopausal status and having no oral contraceptive pills use were factors associated with cytohistologic discrepancy. CONCLUSION: The exact cytohistologic discrepancy rate was relatively high (24.2%). Factors associated with cytohistologic discrepancy were nulliparity and postmenopausal status and having no oral contraceptive pill use.

Fine needle aspiration of thyroid: a cyto-histopathological correlation in Ramathibodi Hospital.

OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) of thyroid lesions in Ramathibodi patients. MATERIAL AND METHOD: A retrospective review is performed on 469 cases of thyroid surgical pathology specimens with previous FNAC reports; during January 2005 to January 2008. All histopathology reports are compared to the latest previous cytopathology results which are categorized as unsatisfactory, benign, inconclusive, borderline and malignancy RESULTS: The cytopathology results showed 74 cases (15.7%) of unsatisfactory specimens, 243 cases (51.8%) of benign lesions, 33 cases (7%) of inconclusive lesions, 15 cases (3.2%) of borderline lesions and 104 cases (22%) of malignant lesions. The histopathology results for benign lesions reveal multinodular and nodular goiter of 236 cases and other diagnosis of 54 cases. The histopathology results for malignant lesions were papillary carcinoma of 147 cases, follicular carcinoma of 24 cases and other malignancy of 8 cases. Among 243 cases of benign from FNAC; 23 cases turn out to be malignancy while 104 cases of malignancy from FNAC show no false positive. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC are 81.9%, 100%, 100%, 90.4% and 93.4% respectively. CONCLUSION: FNAC is a minimally invasive, highly accurate and cost-effective procedure. In our setting the FNAC enable the clinician to "rule-in" malignant lesions with confidence.

Perinatal lethal osteogenesis imperfecta in a Thai newborn: the autopsy and histopathogical findings.

Osteogenesis imperfecta (OI) is an inherited disorder of type I collagen synthesis with an estimate incidence of I in 100,000 live births. Among all types, OI type II is the most severe type with perinatal death. The authors describes a male neonate with characteristic features of osteogenesis imperfect type II, including short crumpling limbs, beaded ribs, poorly bony ossification and blue sclera. Autopsy with histological study revealed not only multiple fractures, but pulmonary hypoplasia and intracerebral hemorrhages were also present. Both are the leading causes of death in the lethal type OI patients.