CHLOROQUINE INDUCED LESIONS IN LIVER OF ALBINO MICE.

A study was carried out to demonstrate the effects of chloroquine on liver of developing albino rats. In this study, 20 white albino mice were used, and distributed in 2 groups. They were kept in the animal house of the College of Veterinary Medicine, their ages ranged between (4-3) months and they were in good health. The first group (G1) was considered a control group, this group included 10 mice who were given regular food in addition to sterilized water daily for a period of (30) days, the second group (G2) included 10 mice, they were given food and water with chloroquine after mixing it in 1ml of distilled water at a dose of 1.2 mg/kg/day for each animal orally for a period of 30 days, it was found that chloroquine induced toxicity in liver tissue of albino mice which were exposed to chloroquine drug for longer during their life. Histological sections of stomach revealed that degenerative cases were present in the mucosa of it and the gastric glands also demonstrated sloughing of its mucus cells, and histological sections of small intestine indicated that the degenerative changes were present in the mucosa and submucosa reflected by sloughing of certain villi and the intestinal glands were also affected, lymphocytic infiltration was present in between the intestinal glands with plasma cells. The present study indicated that the liver tissue was affected by drug used via effect on the histological structure, as there was hypertrophy and degeneration of liver cells, hypertrophy of Kupffer cells in the blood sinusoids.

Serum leptin correlates in fertile and idiopathic infertile Yemeni males: a comparative cross-sectional study.

This comparative cross-sectional study aimed to evaluate the relationship between serum leptin and testosterone, FSH, LH, PRL and semen quality in fertile and idiopathic infertile Yemeni men. A total of 30 infertile males with unknown causes and 30 age-matched healthy fertile males were enrolled in this study. The body mass index (BMI) and waist circumference (WC) were measured. Semen samples were analyzed according to the WHO manual for semen analysis. Serum samples were tested for hormones. Subjects were then divided into subgroups and compared based on their main seminal findings. The WC, serum leptin, PRL, FSH and LH levels were significantly higher (p < 0.05) in the infertile subjects than in the fertile group. Serum leptin demonstrated a significant positive correlation (p < 0.01) with body weight, BMI and WC in fertile males and a significant negative correlation (p < 0.01) with testosterone in fertile and infertile males. Similarly, a significant positive correlation was found between serum leptin and FSH (p < 0.01) and LH (p < 0.05) levels in the infertile subjects. The findings showed that non-obstructive azoospermic (NOA) patients have significant (p < 0.05) high levels of serum leptin, FSH, and LH. These findings may support the possibility of a direct peripheral negative effect of leptin on testicular steroidogenesis independent of the suggested indirect effect, and it could directly impact spermatogenesis without inhibiting testosterone production. This effect was accompanied by increasing serum PRL levels. Furthermore, serum leptin and gonadotropins were found to be increased in the idiopathic NOA group. The present study provided valuable insights into the fertile and idiopathic infertile Yemeni males and could establish an important foundation for future andrological-related studies such as investigating the relationship between leptin and other hormones; and infertility-related genetic and epigenetic factors.

The Impact of Drug-induced Sleep Endoscopy on Therapeutic Decisions in Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

Objective The aim of this study was to assess the ability of drug-induced sleep endoscopy (DISE) to change therapeutic decisions through the identification of obstruction sites in patients with obstructive sleep apnea (OSA). Materials and methods A systematic review and meta-analysis were conducted concerning studies that reported the impact of DISE on therapeutic recommendations. The percentage of change was collected for each study and per site of the collapse. The pooled rate of change and the respective 95% confidence interval (CI) were computed. Subgroup analysis was performed based on patients' age, sample size, the applied DISE protocol, and the originally used diagnostic modality before DISE. Results In a total of nine studies, 1247 patients were included (69.2% males, 59.7% children, 78.04% with a multilevel collapse). Therapeutic decisions changed in 43.69% of patients (CI, 33.84 to 53.54). The change rates were significantly higher in adults (54.0% versus 25.9% in children, P = 0.001), midazolam-based DISE protocols (78.4% versus 48.45% for midazolam plus propofol and 33.9% for propofol, P < 0.001), and after awake endoscopy (62.2% as compared to 44.6% after clinical basic examination [CBE], 40.1% after CBE, lateral cephalometry, and Müller maneuver, P = 0.02). Changes at uvular and palatal sites were more frequent in adults and at the tonsils in children. Conclusion The DISE approach can be promoted via implementing unified classification systems of obstruction sites; the widescale application of target-controlled infusion and its therapeutic benefits can be explored in well-designed randomized studies that compare its efficacy with other diagnostic modalities.

Effect of sample preparation techniques on the concentrations and distributions of elements in biological tissues using µSRXRF: a comparative study.

Routine tissue sample preparation using chemical fixatives is known to preserve the morphology of the tissue being studied. A competitive method, cryofixation followed by freeze drying, involves no chemical agents and maintains the biological function of the tissue. The possible effects of both sample preparation techniques in terms of the distribution of bio-metals (calcium (Ca), copper (Cu) zinc (Zn), and iron (Fe) specifically) in human skin tissue samples was investigated. Micro synchrotron radiation x-ray fluorescence (µSRXRF) was used to map bio-metal distribution in epidermal and dermal layers of human skin samples from various locations of the body that have been prepared using both techniques. For Ca, Cu and Zn, there were statistically significant differences between the epidermis and dermis using the freeze drying technique (p = 0.02, p < 0.01, and p < 0.01, respectively). Also using the formalin fixed, paraffin embedded technique the levels of Ca, Cu and Zn, were significantly different between the epidermis and dermis layers (p = 0.03, p < 0.01, and p < 0.01, respectively). However, the difference in levels of Fe between the epidermis and dermis was unclear and further analysis was required. The epidermis was further divided into two sub-layers, one mainly composed of the stratum corneum and the other deeper layer, the stratum basale. It was found that the difference between the distribution of Fe in the two epidermal layers using the freeze drying technique resulted in a statistically significant difference (p = 0.012). This same region also showed a difference in Fe using the formalin fixed, paraffin embedded technique (p < 0.01). The formalin fixed, paraffin embedded technique also showed a difference between the deeper epidermal layer and the dermis (p < 0.01). It can be concluded that studies involving Ca, Cu and Zn might show similar results using both sample preparation techniques, however studies involving Fe would need more special attention.

Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status.

Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

The evaluation of biologically important trace metals in liver, kidney and breast tissue.

The levels of iron (Fe), copper (Cu), zinc (Zn) and potassium (K) have been measured in normal and malignant liver and kidney tissue using X-ray fluorescence. Zn was reduced in liver and kidney tumours by 63% and 26%, respectively. Fe, Cu and K were increased in kidney tumours by 150%, 8% and 90%, and reduced in liver tumours by 76%, 29% and 43%. A synchrotron microprobe was used to map calcium (Ca), Fe, Cu and Zn in breast tissue. The distributions were compared to reference images and higher concentrations of metals correlated with areas of cancer cells. The average increase of Ca, Fe, Cu and Zn concentrations in areas of malignancy were 70%, 43%, 53% and 87%.

The distribution of trace elements Ca, Fe, Cu and Zn and the determination of copper oxidation state in breast tumour tissue using muSRXRF and muXANES.

A micro beam synchrotron x-ray fluorescence (muSRXRF) technique has been used to determine the localization of metals in primary invasive ductal carcinoma of breast. Nine samples were examined, all of which were formalin fixed tissues arranged as micro arrays of 1.0 mm diameter and 10 microm thickness. Cu was the particular interest in this study although 2D maps of the elements Ca, Fe and Zn, which are also of physiological importance, are presented. The distribution of these metals was obtained at approximately 18 microm spatial resolution and compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cell clusters. Correlations were found between these reference images and the elemental distributions indicating an increase in all element concentrations in the tumour regions of all samples, with the exception of Fe, which in some cases showed a reverse of this trend. On average over all samples the percentage difference from the normal tissue elemental concentrations are Ca approximately 67%, Cu approximately 64% and Zn approximately 145%. Micro x-ray absorption near edge spectroscopy (muXANES) was used to estimate the oxidation state of Cu in 19 normal and 17 tumour regions spread over five samples. The shape and the position of both normal and tumour regions suggest that they contain mixtures of copper ions with a significant fraction of Cu2+. However, the shape of the spectra does not exclude the presence of Cu+. Tumour regions were found to have a higher fraction of Cu+ compared to the normal samples.

Cyclin D1 protein expression in human thyroid gland and thyroid cancer.

Cell cycle progression is facilitated by cyclin dependent kinases (CDKs) that are activated by cyclins, including Cyclin D1 and inhibited by CDK inhibitors. Evidence of the involvement of cyclin gene alterations and over expression of various cyclins in human cancer is growing. The role of Cyclin D1 in malignant progression of papillary carcinomas of the thyroid has yet to be established. We therefore studied the expression of Cyclin D1 protein in thyroid carcinomas of young Kuwaiti patients (36 cases of conventional papillary thyroid carcinoma, 12 cases of its follicular variant, one case of tall cell thyroid carcinoma and one case of medullary carcinoma) using immunohistochemistry. In 23 patients (46%) circumscribed areas of cells were detected that showed a distinct to strong nuclear staining for immunoreactive Cyclin D1 whereas the remaining bulk of the carcinoma cells were negative or only showed a slight cytoplasmic staining. None of the tested clinical or path histological parameters showed a statistically significant correlation with the focal immunostaining. This does not rule out that the detected foci with positive nuclear Cyclin D1 immunostaining are areas where a progressive transformation to a more malignant phenotype occurs which eventually leading to lymph node and distant metastases.

Serum CA-15.3 and CEA patterns in postsurgical follow-up, and in monitoring clinical course of metastatic cancer in patients with breast carcinoma.

Serum CA-15.3 and CEA levels were longitudinally determined in 307 patients with breast carcinoma during postsurgical follow-up and/or therapy. Of 120 patients with no apparent disease, the specificity of marker levels fluctuating within the normal range (true-negative) was 98% for CA-15.3 alone (P = 0.004) and about 88% for CEA alone or for the tests combined. However, the false-negative levels in patients with progressive cancer reduced the predictive value of the tandem to around 76%, i.e. normal levels of both markers correctly predicted uneventful postsurgical course in only three fourths of the patients. Of 187 patients with active disease, the sensitivity of raised or increasing marker levels was around 70% for CA-15.3 alone or CEA alone, and 82% for the tests combined (P = 0.006). The 11% false-positive rate of CEA in patients with no apparent disease decreased the predictive value of a positive test from 98% for CA-15.3 alone (P = 0.006) to 91% for CEA alone or the tandem. Serum CA-15.3 or CEA paralleled the site of relapse: at least one marker was found elevated in 60% of patients with locoregional disease or with metastases to the lungs or bones exclusively, and in 90% of those with metastases to the lungs and bones or to the liver. A concurrent decrease of both marker levels reflected response to therapy while an increase of at least one marker level reflected treatment failure. It may be concluded that the marker tandem was better than either marker alone for follow-up aimed at detection of relapse, and that the tests were approximately 80% accurate for follow-up and/or monitoring therapy.

Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors.

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.