Biomechanical impact of meniscal ramp lesions on knee joint contact characteristics in ACL deficient knees: a cadaveric analysis.

PURPOSE: To evaluate the changes in contact characteristics of the tibiofemoral joint resulting from a meniscal ramp lesion in the medial meniscus. METHODS: Twelve cadaveric knees (six matched pairs) were subjected to a 600 N axial load using a custom testing jig, which allowed for knee positioning at 0°, 45°, and 90° of flexion without other constraints. The knees were randomly assigned to either a ramp lesion group (n = 6) or a posterior root lesion group (n = 6). Four testing conditions were examined: (1) intact, (2) isolated ramp lesion, (3) isolated posterior root tear of the medial meniscus, and (4) combined ramp lesion and posterior root tear of the medial meniscus. Contact characteristics were evaluated using a flexible pressure sensor, the I-Scan System. RESULTS: Peak contact pressure in isolated ramp lesions (4.15 ± 0.98 MPa, P = 0.206) showed non-significant increases compared to the intact condition (3.86 ± 1.32 MPa). Peak contact pressure in isolated posterior root tears (4.58 ± 1.70 MPa, P = 0.040) and, combined ramp and posterior root lesions (4.67 ± 1.47 MPa, P = 0.003) were significantly higher than that in the intact condition. The knee flexion position significantly affected the medial tibiofemoral joint's contact area, contact pressure, and peak contact pressure (P < 0.001 for all). CONCLUSION: Isolated ramp lesions did not significantly impact force transmission, contact area, or contact pressure. In contrast, isolated root lesions and combined ramp and posterior root tears of the medial meniscus significantly intensified the changes in contact characteristics in the medial tibiofemoral joint compared to the intact condition. LEVEL OF EVIDENCE: Level III.

Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats.

This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the AT1R/Nox4 cascade in 2K-1C hypertension.

Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet.

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague-Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

Clitoria ternatea L. extract prevents kidney damage by suppressing the Ang II/Nox4/oxidative stress cascade in l-NAME-induced hypertension model of rats.

Clitoria ternatia L. (CT) has been reported to have anti-inflammatory and antioxidant effects. This study investigated the effect of CT aqueous flower extract on blood pressure and renal alterations in Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Male Sprague Dawley rats received l-NAME in drinking water and were treated with CT flower extract or lisinopril. CT aqueous flower extract and lisinopril alleviated l-NAME-induced hypertension (p < 0.05). Glomerular extracellular matrix accumulation, renal fibrosis, and increased serum creatinine levels were observed in l-NAME-induced hypertensive rats and attenuated by CT flower extract or lisinopril co-treatment (p < 0.05). High levels of plasma angiotensin II (Ang II) and upregulated nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) protein expression in the kidneys induced by l-NAME were alleviated by CT flower extract or lisinopril co-treatment (p < 0.05). Furthermore, CT flower extract and lisinopril treatment reduced lipid peroxidation and elevated plasma and kidney malondialdehyde levels in l-NAME-induced hypertensive rats (p < 0.05). In conclusion, CT flower extract prevented l-NAME-induced renal injury and dysfunction in rats. The possible mechanism may be related to the suppression of Ang II-mediated Nox4 expression and the oxidative stress cascade in rats.

Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome.

BACKGROUND: Hesperidin has been reported to have biological activities such as antihypertensive, hypoglycemic, and antioxidant effects. This study investigated whether hesperidin could improve signs of the metabolic syndrome and cardiac function in a high-fat diet (HFD) induced metabolic syndrome (MS) in rats. METHODS: Male Sprague-Dawley rats were fed HFD and 15% fructose for 16 weeks and treated with hesperidin (15 or 30 mg/kg, based on signs of MS from a preliminary study) or metformin, a positive control agent, (100 mg/kg) for the final four weeks. Cardiac function, blood pressure, fasting blood glucose, oral glucose tolerance, serum insulin, and lipid profiles were measured. Histomorphometrics of left ventricles, epidydimal fat pads and liver were evaluated. Expressions of phosphorylate insulin receptor substrate1(p-IRS1), p-Akt and GLUT4 in cardiac tissue were determined. RESULTS: Hesperidin and metformin attenuated MS in HFD rats (p < 0.05). The accumulation of visceral fat pads and fatty liver associated with increases in liver lipid contents and liver enzymes were found in MS rats that were alleviated in hesperidin or metformin-treated groups (p < 0.05). Hesperidin and metformin improved cardiac dysfunction and hypertrophy observed in MS rats (p < 0.05). Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05). Hesperidin (30 mg/kg) was more effective than the lower dose. CONCLUSION: Hesperidin was effective in reducing signs of MS and alterations of LV hypertrophy and function. These beneficial effects on the heart were associated with the restoration of the cardiac insulin signaling pathway in MS rats.

Implication of RAS in Postnatal Cardiac Remodeling, Fibrosis and Dysfunction Induced by Fetal Undernutrition.

Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum, and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-ß1 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-ß1 tended to be higher, and the end-diastolic diameter and E/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions. In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction.

Tangeretin ameliorates erectile and testicular dysfunction in a rat model of hypertension.

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT1R) and gp91phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT1R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT1R/gp91phox expressions and testicular eNOS and StAR expression.

Nobiletin alleviates vascular alterations through modulation of Nrf-2/HO-1 and MMP pathways in l-NAME induced hypertensive rats.

Nobiletin, a citrus flavonoid, exhibits a wide range of biological activities. This study investigated the effect of nobiletin on vascular dysfunction and remodeling in l-NAME-induced hypertensive rats. Male Sprague-Dawley rats were given l-NAME (40 mg kg-1) for five weeks to induce hypertension and treated with nobiletin (20 or 40 mg kg-1) or captopril (5 mg kg-1) for the last two weeks. Nobiletin or captopril significantly reduced blood pressure and the enhancement of the contractile response to sympathetic nerve stimulation in the mesenteric vascular beds of l-NAME rats (p < 0.05). Both agents improved the impairment of vasorelaxation responses to acetylcholine in mesenteric vascular beds and aortic rings in l-NAME rats (p < 0.05). Moreover, nobiletin and captopril decreased oxidative stress markers, restored the abnormality of plasma NOx and the protein expressions of eNOS, Nrf-2 and HO-1 observed in l-NAME rats (p < 0.05). Increases in aortic wall thickness, cross sectional area, vascular smooth muscle cells and collagen deposition that occurred in l-NAME rats were reduced by nobiletin or captopril (p < 0.05). These reductions were associated with the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 protein expression (p < 0.05). These findings indicated that nobiletin had antihypertensive effects with amelioration of vascular alterations. The molecular mechanism is likely to involve the restoration of Nrf-2/HO-1/MMP signaling pathways.

Predetermining glenoid dimensions using the scapular dimensions.

BACKGROUND: Variations of morphology of the glenoid cavity have been previously reported. These influence the surgical reconstruction or arthroplasty of the shoulder. This study aims to study the variation of the shape of suprascapular notch, shape of glenoid cavity, dimensions of both the scapular and the glenoid cavity, and predict the glenoid dimensions from the scapular dimension parameters. MATERIALS AND METHODS: Adult-dried scapulae were collected. The shapes of each suprascapular notch and glenoid cavity were evaluated. The scapular height, scapular width, glenoid superoinferior distance, and glenoid anteroposterior distance were measured using a digital vernier caliper, and statistical analysis was conducted on the data that were obtained. RESULTS: There were 264 scapulae included in this study (166 male and 98 female). Most of the glenoid cavities were pear shaped (69.7%). The two most common types of suprascapular notches were small depression notches (31.8%) and the absence of notches (25.8%). The mean ± SD of scapular height, scapular width, glenoid superoinferior distance, and glenoid anteroposterior distance were 148.2 ± 10.0, 108.1 ± 6.4, 37.1 ± 2.2, and 27.4 ± 2.1 mm, respectively, in the male samples and 133.0 ± 7.0, 97.0 ± 5.2, 33.2 ± 1.9, and 23.7 ± 1.7 mm, respectively, in the female samples. The male scapulae were significantly larger than the female scapulae (p value < 0.05). However, there were no differences between the male and female scapulae in terms of scapular index or glenoid index (p value > 0.05). Scapular height and width were significantly associated with both the glenoid superoinferior distance (p = 0.0001) and glenoid anteroposterior distance (p value = 0.0001). CONCLUSION: Scapular height and width can predict the dimensions of the glenoid. In cases of glenoid bone loss or shoulder arthroplasty, the native normal glenoid dimensions can be determined from the scapular dimensions as visualized using a true scapular anteroposterior radiograph. The surgeon can use these preoperative parameters when performing glenoid reconstruction or shoulder arthroplasty.

Carthamus Tinctorius L. extract attenuates cardiac remodeling in L-NAME-induced hypertensive rats by inhibiting the NADPH oxidase-mediated TGF-ß1 and MMP-9 pathway.

Carthamus tinctorius L. (CT) has been widely used in Asian countries as a beverage and a folk medicine. The current study investigates the effect of CT extract on cardiac remodeling and possible mechanisms involved in Nw-nitro-l-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were administrated with L-NAME (40mg/kg/day) for five weeks to induce hypertension. Hypertensive rats were treated with CT extract (300mg/kg/day) or captopril (5mg/kg/day) or vehicle for a further two weeks. Treatment of hypertensive rats with CT extract or captopril significantly decreased systolic blood pressure, left ventricular (LV) hypertrophy and fibrosis, small intramyocardial coronary artery remodeling, and cardiac weight index. CT extract or captopril increased plasma nitric oxide metabolite (NOx) levels and reduced plasma transforming growth factor ß1 (TGF-ß1) level, together with downregulation of cardiac TGF-ß1 and matrix metalloproteinases-9 (MMP-9) expression. In addition, decreased plasma malondialdehyde (MDA) levels, consistent with downregulation of NADPH oxidase subunit gp91phox expression in heart tissue, was also observed after CT extract or captopril treatment. These findings suggest that CT extract alleviates cardiac remodeling in L-NAME-induced hypertensive rats, which is possibly related to inhibition of the NADPH oxidase-mediated TGF-ß1-MMP-9 pathway.

Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-ß1 and MMPs Protein Expression.

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by n-nitro l-arginine methyl ester (l-NAME) in rats. Male Sprague-Dawley rats were treated with l-NAME (40 mg/kg), l-NAME plus hesperidin (15 mg/kg), hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in l-NAME rats. l-NAME-induced cardiac remodeling, i.e., increases in wall thickness, cross-sectional area (CSA), and fibrosis in the left ventricular and vascular remodeling, i.e., increases in wall thickness, CSA, vascular smooth muscle cells, and collagen deposition in the aorta were attenuated by hesperidin or captopril. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-ß1), and enhancing plasma nitric oxide metabolite (NOx) in l-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF- ß1 protein expression and the overexpression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was suppressed in l-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in l-NAME hypertensive rats. The possible mechanism may involve antioxidant and anti-inflammatory effects.

Hesperidin Suppresses Renin-Angiotensin System Mediated NOX2 Over-Expression and Sympathoexcitation in 2K-1C Hypertensive Rats.

Hesperidin, a flavonoid derived from citrus fruits, possesses several beneficial effects including anti-oxidation and anti-inflammation. The aim of this study was to investigate the effects of hesperidin on the renin-angiotensin system (RAS) cascade that mediated oxidative stress and sympathoexcitation in two-kidney, one-clipped (2K-1C) hypertensive rats. 2K-1C hypertension was induced in male Sprague-Dawley rats. Hypertensive rats were treated with hesperidin at 20[Formula: see text]mg/kg or 40[Formula: see text]mg/kg or losartan at 10[Formula: see text]mg/kg beginning at three weeks after surgery and then continued for four weeks ([Formula: see text]/group). Hesperidin reduced blood pressure in a dose-dependent manner in hypertensive rats compared to untreated rats ([Formula: see text]). Increased plasma angiotensin converting enzyme (ACE) activity and angiotensin II levels, as well as, upregulated AT1 receptor protein expression in aortic tissues were attenuated in hypertensive rats treated with hesperidin. Hesperidin suppressed oxidative stress markers and NADPH oxidase over-expression, and restored plasma nitric oxide metabolites in 2K-1C rats. This was associated with improvement of the vascular response to acetylcholine in isolated mesenteric vascular beds and aortic rings from 2K-1C rats treated with hesperidin ([Formula: see text]). Enhancement of nerve-mediated vasoconstriction related to high plasma noradrenaline in the 2K-1C group was alleviated by hesperidin treatment ([Formula: see text]). Furthermore, losartan exhibited antihypertensive effects by suppressing the RAS cascade and oxidative stress and improved vascular dysfunction observed in 2K-1C rats ([Formula: see text]). Based on these results, it can be presumed that hesperidin is an antihypertensive agent. Its antihypertensive action might be associated with reducing RAS cascade-induced NOX2 over-expression and sympathoexcitation in 2K-1C hypertensive rats.

Carthamus tinctorius L. extract improves hemodynamic and vascular alterations in a rat model of renovascular hypertension through Ang II-AT1R-NADPH oxidase pathway.

Carthamus tinctorius L. (CT) is widely used in Asian countries as a beverage and in folk medicine. The effects of CT extract on hemodynamics, vascular remodeling, the renin-angiotensin system (RAS) and oxidative stress in the two-kidney, one clip (2K-1C) hypertensive rat model were investigated. Renovascular hypertension was induced in male Sprague-Dawley rats and were treated with CT extract (500mg/kg/day) or captopril (5mg/kg/day) or vehicle for four weeks. CT extract or captopril reduced blood pressure, hindlimb vascular resistance, and increased hindlimb blood flow in 2K-1C hypertensive rats (p<0.05). Increases in aortic wall thickness, cross-sectional area and collagen deposition in 2K-1C rats were alleviated with CT extract or captopril treatment (p<0.05). CT extract or captopril suppressed RAS activation, including elevated serum ACE activity, and plasma Ang II level and up-regulated aortic AT1R protein expression in 2K-1C rats (p<0.05). Furthermore, CT extract or captopril reduced vascular superoxide production, aortic NADPH oxidase subunit gp91phox expression and increased plasma nitric oxide metabolite levels in 2K-1C rats (p<0.05). These findings suggest that CT extract ameliorated hemodynamic alteration and vascular remodeling in 2K-1C hypertensive rats. Possible mechanisms may involve RAS inhibitor effects and potent antioxidant activity.

Classification and incidence of pterion patterns of Thai skulls / Clasificación e incidencia de los patrones de pterion en cráneos de Tailandia

SUMMARY: The pterion, a landmark for neurosurgery, is the weakest part of the skull owing to relatively thin bone. Variant patterns of pterion can confuse the clinicians during diagnosis of the lateral skull fractures in emergency situations. Thedifferent pterion types of many races have been reported but not of Thais. In this study; therefore, we investigated the incidence of sutural pterion patterns on of Thai skulls. The infratemporal fossa of 110 sides from 55 dried skulls identified as Thais were observed and classified for individual pterion types. The results showed that the pterion patterns can be classified into 4 types; spheno-parietal (87.27 %), fronto-temporal (4.55 %), uni-epipteric (6.36 %), and multi-epipteric (1.82 %) types. It was found that the spheno-parietal type was dominant in males (61.81 %) than in females (25.45 %). The majority of the skulls showed bilateral symmetry (85.45 %) in all types and the unilateral ones were far less (14.55 %). In bilateral pterion incidence, the spheno-parietal type was approximately 93.61 % while the uni-epipteric type was not found. Moreover, the bilateral multi-epipteric type was found only in one female skull (2.13 %). These findings will be useful for the radiologists and the neurosurgeons concerning lateral skull fractures in emergency diagnosis.

RESUMEN: El pterion es un punto de referencia para la neurocirugía, y es la parte más débil del cráneo debido a estar conformado por hueso relativamente delgado. Los diversos patrones de pterion pueden confundir a los clínicos durante el diagnóstico de fracturas laterales de cráneo en situaciones de emergencia. Con excepción de los tailandeses, diferentes tipos de pterion se han reportado en muchas razas. hemos investigado la incidencia de diversos patrones de pterion en cráneos de Tailandia. Analizamos 110 fosas infratemporales, correspondientes a 55 cráneos secos del Noreste de Tailandia y se clasificaron de acuerdo al tipo de pterion. Los resultados mostraron que el pterion puede clasificarse en 4 tipos: esfeno-parietal (87,27 %), fronto-temporal (4,55 %), epiptérico (3,63 %) y multi-epiptérico (1,81 %). Se encontró que el tipo esfeno-parietal tuvo mayor incidencia en hombres (61,81 %) que en mujeres (25,45 %). Además, la incidencia de simetría bilateral (85,45 %) fue mayor que la unilateral (14,55 %). A nivel bilateral, el tipo esfeno-parietal fue de 93,61 %, mientras que el tipo epiptérico no se observó. Por otra parte, el tipo multiepiptérico fue encontrado bilateralmente en un solo cráneo femenino (2,13 %). Esta incidencia puede ser utilizada como un conocimiento básico para los radiólogos tailandeses sobre las fracturas laterales del cráneo en un diagnóstico de emergencia.

A large modern Southeast Asian human skeletal collection from Thailand.

The Khon Kaen University Human Skeleton Research Centre has a large human collection consisting of 745 modern northeastern Thai (Isan) skeletons derived from bodies bequeathed to the Department of Anatomy during the period 1979-2014. The aim of this paper is to document the collection and address the question of whether the collection may be representative of local Isan people, or populations of the wider region of mainland Southeast Asia. This will determine its value as a reference collection for forensic anthropology in particular but also for all other fields of research about human skeletal biology. Sex is recorded for 99.6% of the skeletons, and age at death for 91.7%. The collection consists of two-thirds males, one-third females. It includes 10 individuals less than 19 years of age, and adults ranging in age from 20 to 109 years of age. Average age at death is 62 years. Other data available for smaller proportions of the collection include cause of death, occupation, and height and weight at the time of donation. Dates of birth are estimated to range from the late 19th Century to the most recent in 1988. Analysis of the demographic composition of the collection shows that is likely to be representative of the ancestral mix of the Isan people, and of the village farmers who still form a large portion of the Isan population. It may also represent 20th Century populations of much of Southeast Asia where agriculture dominates the economy. The collection forms a valuable resource for research on regional human skeletal characteristics for use in forensic anthropology.

Effect of asiatic acid on the Ang II-AT1R-NADPH oxidase-NF-κB pathway in renovascular hypertensive rats.

Asiatic acid, a triterpenoid compound derived from Centella asiatica, has been demonstrated to have antioxidant and anti-inflammatory effects. The present study evaluated the effects of asiatic acid on hemodynamic alterations, renin-angiotensin system (RAS), oxidative stress, and inflammation in 2K-1C hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats and treated with vehicle, asiatic acid (30 mg/kg/day), or captopril (5 mg/kg/day) for 4 weeks. We observed that 2K-1C hypertensive rats exhibited hemodynamic alterations such as high blood pressure, heart rate, hindlimb vascular resistance, and low hindlimb blood flow. Signs of RAS activation, such as increased plasma angiotensin II and serum angiotensin-converting enzyme activity, enhanced AT1R protein expression, and suppressed AT2R expression was observed in 2K-1C hypertensive rats. Overproduction of vascular superoxide, high levels of plasma MDA, low levels of plasma nitric oxide metabolites (NOx), and upregulation of gp91phox protein expression were observed in hypertensive rats. Furthermore, inflammation was observed in hypertensive rats, as evidenced by increased plasma TNF-α, NF-κB, and phospho-NF-κB protein expression. Asiatic acid or captopril alleviated hemodynamic alterations, RAS activation, oxidative stress, and inflammation in 2K-1C hypertensive rats. These findings indicate that asiatic acid is an antihypertensive agent that ameliorates hemodynamic alterations in 2K-1C hypertensive rats. This effect may involve one or both of the following mechanisms: the direct effect of asiatic acid on RAS activation, oxidative stress and inflammation, and/or asiatic acid acting as an ACE inhibitor agent to inhibit the Ang II-AT1R-NADPH oxidase-NF-κB pathway.

Garcinia mangostana pericarp extract protects against oxidative stress and cardiovascular remodeling via suppression of p47phox and iNOS in nitric oxide deficient rats.

Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension and cardiovascular remodeling are associated with oxidative stress and inflammation. Garcinia mangostana Linn., has been reported to have antioxidant and anti-inflammatory properties. This study investigated whether G. mangostana pericarp extract (GME) could prevent l-NAME-induced hemodynamic alterations, cardiovascular remodeling, oxidative stress and inflammation in rats. Male Sprague-Dawley rats were given 40mg/kg/day of l-NAME in drinking water to induce hypertension, and were simultaneously treated with GME at a dose of 200mg/kg/day. Rats that received l-NAME for five weeks had high blood pressure, left ventricular hypertrophy and thickening of aortic wall. Vascular superoxide production, plasma malondialdehyde (MDA), and plasma tumor necrosis factor alpha (TNF-α) were significantly increased in l-NAME-hypertensive rats (p<0.05). This was consistent with up-regulation of the p47phox NADPH oxidase subunit and iNOS protein expression in aortic tissues (p<0.05). Low levels of plasma nitric oxide metabolites were observed in l-NAME hypertension. GME prevented the development of hypertension and cardiovascular remodeling induced by l-NAME with reduced oxidative stress and inflammation. These data suggest that GME had a protective effect against l-NAME-induced hypertension and cardiovascular remodeling via suppressing p47phox NADPH oxidase subunit and iNOS protein expression resulting in enhancing NO bioavailability.

Monitoring the biochemical alterations in hypertension affected salivary gland tissues using Fourier transform infrared hyperspectral imaging.

Fourier transform infrared spectroscopy (FTIR) imaging has been applied to investigate biochemical differences between salivary glands from control and hypertensive rats. Male Sprague-Dawley rats were divided into two groups including a control group and another hypertension group that were treated orally, with N-nitro-l-arginine methyl ester (l-NAME) via drinking water for 3 weeks to develop hypertension. In the control group, rats were treated with only drinking water for 3 weeks. The formalin-fixed paraffin embedded tissue specimens from submandibular and sublingual glands were analysed with a FTIR focal plane array imaging spectrometer and multi-composite images of all tissue sections were analysed simultaneously using Unsupervised Hierarchical Cluster Analysis (UHCA) and the extracted spectra were further analysed using Partial Least Squares Discriminant Analysis (PLS-DA). In general, hypertension affected salivary gland tissues were characterised by higher concentrations of triglycerides as evidenced by an increase in the 1745 cm-1 band. Higher concentrations of carbohydrates and proteins were also observed in the hypertensive group along with a decrease in bands associated with nucleic acids. PLS-DA scores plots provided good differentiation in sublingual gland tissues between control (n = 3734 spectra) and hypertension (n = 4538) and also in submandibular gland tissues between control (n = 5051) and hypertension (n = 4408). We have shown that FTIR imaging can be used to differentiate the macromolecular information between physiological and pathological conditions in tissue biopsy specimens. In the next phase, we will investigate the infrared predictive markers of hypertension in biofluids including serum and saliva using attenuated total refection spectroscopy.

Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine.

Kaempferia parviflora extract ameliorates the cognitive impairments and the reduction in cell proliferation induced by valproic acid treatment in rats.

Kaempferia parviflora is a herbal plant whose rhizomes are used in traditional medicine. Investigations of this plant have shown it to have antidepressant activity and to improve learning and memory in animal models. The aim of the present investigation was to determine whether K. parviflora could protect the brain from the impairments in cognition and hippocampal neurogenesis which are caused by valproic acid (VPA). Male Sprague Dawley rats (180-200g) were given once daily K. parviflora extract (100mg/kg) via oral gavage for 21 days. Rats received twice daily intraperitoneal injections of valproic acid (300mg/kg) from days 8 to 21 of the experiment. Spatial memory was tested using the novel object location (NOL) test five days after the end of treatment. Cell proliferation in the sub granular zone (SGZ) of the dentate gyrus was quantified by immunohistochemistry and levels of doublecortin (DCX) were determined by Western blotting. Co-treatment of VPA and K. parviflora prevented the cognitive decline and reduction in proliferating cells caused by VPA. Furthermore, co-treatment significantly increased DCX protein levels within the hippocampus. These findings demonstrate that K. parviflora is able to prevent the brain from VPA-induced the impairments of spatial memory and proliferating cells within the SGZ.