Histomorphological, Histochemical and Ultrastructural Studies on the Healthy Liver of Yemen Veiled Chameleon (Chamaeleo calyptratus) in Southern Saudi Arabia / Estudios Histomorfológicos, Histoquímicos y Ultraestructurales en el Hígado Sano del Camaleón Velado de Yemen (Chamaeleo calyptratus) en el Sur de Arabia Saudita

SUMMARY: The livers of reptiles are being studied as a model for the link between the environment and hepatic tissue. There have been few investigations on the histology of reptile livers, and very few or no studies have examined the histology of liver of veiled chameleon (Chamaeleo calyptratus). This paper describes the histomorphological, histochemical and ultrastructural characterization of the liver of veiled chameleons in southern Saudi Arabia. Seven Chamaeleo calyptratus were captured in the summer season in Abha City, Aseer region, southern Saudi Arabia. Chamaeleon liver samples were processed for histomorphology, histochemistry and ultrastructure analyses. Morphologically liver of Chamaeleo calyptratus was observed as a large dark brown organ with lighter speckles, which represent melanin deposits. It located at the ventral part of abdominal cavity forward of the stomach. Its dimensions approximately were 3.7 x 2 cm. The liver was a bilobed organ divided into two lobes, right and left lobes. The right one was bigger than the others. The gallbladder was well developed and had an elongated shape, situated between the two lobes and contained the bile for the digestion. Microscopically, the liver was found to be covered by a thick layer of connective tissue, which formed the hepatic capsule. Hepatic parenchyma probably appeared in cross sections as hepatic glandular-like alveoli "acini" or follicular structures with various diameters, each acinus contains approximately four to six hepatocytes, surrounded by sinusoidal capillaries filled with abundant melanomacrophages, which are absent in birds and mammals. Melanomacrophages are common in the hepatic parenchyma's perisinusoidal areas, particularly near portal spaces. Hepatocytes are polyhedral or pyramidal with and mostly contained large, rounded nuclei mostly peripherally located, with prominent dark oval nucleoli. Some of nuclei are eccentric or central position. The cytoplasm appeared spongy or vacuolated and more eosinophilic when stained by hematoxylin-eosin and strongly reactive to PAS staining technique, indicating abundant glycogen content. The reticular fibers that surround hepatocytes, blood arteries, and sinusoids supported the hepatic parenchyma. The blood sinusoids are seen interspersed among hepatocytes of varying sizes. The sinusoidal lumen was bordered by flattened endothelial cells and includes elliptical nucleated erythrocytes and liver macrophages as phagocytes, which are also known as Kupffer cells. Branches of the portal vein, hepatic artery, small bile duct, and lymph vessels were detected in the hepatic portal area "tract" or triad which made up of connective. Hematopoietic tissue was observed in subcapsular region and portal triads. Ultrastructurally, the hepatocyte appeared polyhedric containing a single large rounded basal or eccentric vesicular nucleus with prominent nucleolus. Extensive network of rough endoplasmic reticulum (RER) often arranged in an array parallel to the nuclear membrane with many mitochondria, and Golgi apparatus were described. The cytoplasm contained glycogen granules, vesicles or vacuoles scattered throughout the cytoplasm especially at the apical region were reported. The bile canaliculi and the hepatic "Kupffer" cells were also discussed. This is the first study on the histological characterization of the healthy liver of Yemen veiled chameleon in southern Saudi Arabia. The findings reported here should be used as a reference to compare with the pathological abnormalities of the liver in this animal.

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Malignant, fungating giant-cell tumor of the tendon sheath (GCT-TS) of the foot: A case report.

Giant-cell tumors of the tendon sheath (GCT-TS) are relatively common benign tumors that arise in close proximity to joints and tendons. Malignant GCT-TS are extremely rare. Surgery with wide resection remains the cornerstone for treating malignant giant-cell tumors of the tendon sheath especially in large tumor cases.

An Unusual Solitary Fibrous Tumor of the Ischiorectal Region.

Solitary fibrous tumors (SFTs) are rare fibroblastic/myofibroblastic proliferations that occur in a wide range of anatomical sites. These tumors have nonspecific clinical presentations often with unpredictable biological behavior. SFTs can be slow growing low-risk tumors or rapidly growing high-risk tumors. They show a wide variety of histological features and typically are characterized by NAB2-STAT6 fusion. SFTs of the ischiorectal fossa are rare, with few studies reported in the literature to date. Here, we report a 90-year-old male who had a road traffic accident in October 2018. A pelvic computed tomography (CT) revealed a mass measuring 3.5 × 2.5 cm in the right ischiorectal fossa. Histopathology of the CT-guided biopsies confirmed the diagnosis of low-grade SFT. No surgical intervention was needed since the patient was asymptomatic. In January 2022, a follow-up CT showed a gradual increase in tumor size (5 × 3.5 × 3 cm), but not infiltrating the surrounding structures. However, the patient complained of constipation, which warranted a surgical excision of the mass. Subsequently, immunohistological examination reconfirmed the diagnosis of low-risk SFT. Here, we discussed the clinicopathological features of the case and the relevant literature about pelvic SFTs. In conclusion, SFTs should be considered in the differential diagnosis of any ischiorectal mass. It is recommended that tissue samples be obtained, and immunohistology should be performed.

Wide resection and reconstruction in a low resource area, cemented nail technique knee arthrodesis; a report of case and surgical technique.

INTRODUCTION AND IMPORTANCE: Osteosarcomas are primary malignant bone tumors that are driven from bone-forming mesenchymal cells and account for nearly 20 % of primary bone tumors. CASE PRESENTATION: A 16-year-old female presented with chief complaint of pain and swelling on her right knee for 6 months with history of trauma. Her knee mobility and ROM was limited due to pain and the mass. Physical examination revealed a 15 × 22 cm mass on distal part of right femur with visible dilated veins. There was normal distal motor, sensory functions. Imaging revealed distal femur mass with mixed lytic and blastic features, wide transitional zone with hair and periosteal reaction; features suggestive of osteosarcoma that was confirmed by histopathological examinations as intramedullary osteosarcoma. She undergone surgical treatment consisting of surgical excision of the mass with safety margins and knee reconstruction by knee arthrodesis using femoral-nail and bone cement technique with excellent outcome. CLINICAL DISCUSSION: Osteosarcoma is best investigated through plain imaging, MRI and possible CT with histology being confirmatory. It is best approached with meticulous dissection to ensure clear margins or if necessary, amputation. Following resection, reconstruction can be done. In this specific case, the tumor was on the distal femur and the underlying knee was arthrodesed using cemented nail technique in which a cemented intramedullary nail was inserted with excellent clinical outcome. CONCLUSION: Surgical approach to osteosarcoma can be performed through limb salvage or amputation. Arthrodesis with cemented nail technique using an intramedullary nail can be performed in some patients with excellent clinical outcome.

Ultrastructure abnormalities of collagen and elastin in Arab patients with arterial tortuosity syndrome.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disease characterized by elongation and tortuosity of the large- and medium-sized arteries. ATS patients display features that are also found in Ehlers-Danlos syndrome (EDS) patients. ATS is caused by pathogenic mutations in the SLC2A10 gene, which encodes for the glucose transporter, GLUT10. This study aimed at examining the ultrastructure of skin for abnormalities that can explain the loose skin and arterial phenotypes of Arab patients with the p.S81R mutation in SLC2A10. Forty-eight patients with SLC2A10 mutation were recruited for this study. Skin biopsy specimens from three children with ATS and a healthy child were examined by electron microscopy to determine the ultrastructure of collagen and elastin. Histopathologic staining of sections from tissue biopsy specimens was also performed. Large spaces were observed among the collagen fibrils in the skin biopsy specimens obtained from ATS patients, suggesting disorganization of the collagen structures. Furthermore, elastin fiber contents and their thickness are reduced in the skin. In small muscular arteries in the skin from ATS patients, discontinuous internal elastic lamina, lack of myofilaments, and disorganized medial smooth muscle cells with vacuolated cytoplasm are present. The disorganization of collagen fibrils and reduced elastin contents in the skin may explain the loose skin phenotype of ATS patients similar to the EDS patients. The lack of elastin in small muscular arteries may have contributed to the development of arterial tortuosity in these patients.

A Unique Coexistence of Rectal Adenocarcinoma and Gastric Antral Gastrointestinal Stromal Tumor: A Case Report and Minireview.

Several studies have reported the coexistence of gastric gastrointestinal stromal tumors (GISTs) with many primary carcinomas such as gastric and renal cell carcinomas. However, to date reports about the coexistence of gastric GISTs and colorectal adenocarcinoma are limited. Herein we report a unique case of gastric GIST coexisting synchronously with rectal adenocarcinoma in a 36-year-old male patient who presented with weight loss, vomiting, and bleeding per rectum. Computed tomography (CT) revealed circumferential rectal mass coexistent with an irregular gastric soft tissue mass. The diagnosis of rectal adenocarcinoma and gastric GIST was established by immunohistological evaluation of the colonoscopic (rectum) and CT-guided (stomach) biopsies. The patient received concomitant chemoradiotherapy for the rectal adenocarcinoma and neoadjuvant imatinib for the gastric GIST. This was followed by low anterior resection with total mesorectal excision and wedge resection of the gastric mass. Follow-up of the patient for 1.5 years revealed no evidence of disease recurrence. We also present a minireview of the literature that provides insights into this subject as a separate section.

Effects of various doses of glutathione on the proliferation, viability, migration, and ultrastructure of cultured human melanocytes.

Normal human cultured melanocytes were exposed to various glutathione concentrations (0.1, 0.5, 1.0, 5.0, and 10.0 mg/mL) for 72 hours. At the end of the experiment, proliferation, viability, migration, and ultrastructural changes were monitored. Glutathione at the doses of 0.5 to 10.0 mg/mL reduced the viability of melanocytes significantly as compared to the control (P < .05). Glutathione significantly reduced the proliferation of melanocytes at the doses of 0.5 to 10.0 mg/mL as compared to the control (P < .001). Glutathione at 0.5 to 10.0 mg/mL significantly reduced the migration of melanocytes as compared to the control (P < .001). The percentage of mature melanosomes was 53.43% in control and 50.58%, 41.83%, 33.4%, and 8.95% in 0.1, 0.5, 1.0, and 5.0 mg/mL glutathione exposed cells, respectively. This reduction in the number of mature melanosomes was statistically significant as compared to the control. However, no cytotoxic effects were recognized by electron micrographs. These results encourage the potential implementation of glutathione as a skin-lightening agent. However, this study is limited by cell culture and ultrastructural. It should therefore be expanded in the future to include patients with pigmentary disorders.

Safety and efficacy of parenteral glutathione as a promising skin lightening agent: A controlled assessor blinded pharmacohistologic and ultrastructural study in an animal model.

Hyperpigmentation was induced in the skin of experimental animals using UVB at 6 J/cm2 three times a week for three consecutive weeks. Subsequently, glutathione was injected intraperitoneally in the experimental animals at doses of 10, 20, and 40 mg/kg body weight three times a week for three consecutive weeks. At the end of the experiment, blood samples and lung, kidney, liver, and skin tissue specimens were collected from animals for hematological, biochemical, histological, and electron microscopy examination. Glutathione at 40 mg/kg body weight/day reduced skin hyperpigmentation significantly, except at low doses. The skin lightening effect assessed by a chromameter was dose-dependent. There were no statistically significant differences among the mean values of AST, ALT, creatinine, BUN, and CBC counts across the four groups. Lung, kidney, and liver tissue specimens did not show any histological toxic changes. The number of melanin granules was significantly lower in the group treated with the highest dose of glutathione compared to that in the control. Electron microscopy proved that glutathione at 20 and 40 mg/kg body weight/day was able to reduce the number of melanized cells significantly compared to that in the control. Parenteral glutathione was effective as a skin lightening agent and did not provoke any toxic effects in the employed animal model. The limitation of the study was conducted in guinea pigs and was of short-term duration.

Apoptotic Induction and Anti-Migratory Effects of Rhazya Stricta Fruit Extracts on a Human Breast Cancer Cell Line.

Rhazya stricta is a medicinal plant that is widely used in Saudi folklore medicine for treatment of various diseases. R. stricta fruit powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, and methanol using a Soxhlet extractor. The cytotoxic effects of these fractions on human breast cancer cells (MDA-MB-231 and MCF-7) and non-tumorigenic control cells (MCF-10A) were evaluated via cell viability measurements, microscopy, gene expression, and migration assays. Moreover, the effect of the most promising extract on 7,12-dimethyl-benz[a]anthracene (DMBA)-induced breast cancer was investigated in rats. The promising extract was also subjected to gas chromatography-mass spectrometry. Fruit extracts of R. stricta were significantly cytotoxic toward all tested cell lines, as demonstrated by MTT and LDH assays. Treatment of MDA-MB-231 cells with fruit ethyl acetate fraction (RSF EtOAc) increased expression 11of P53, Bax and activation of caspase 3/7. A cell migration scratch assay demonstrated that extracts at non-cytotoxic concentrations exerted a potent anti-migration activity against the highly invasive MDA-MB-231 cell line. Moreover, RT-PCR results showed that RSF EtOAc significantly downregulated MMP-2 and MMP-9 expression, which play an important role in breast cancer metastasis. Histological studies of breast tissue in experimental animals showed a slight improvement in tissue treated with fruit ethyl acetate extract. GC-MS chromatogram showed thirteen peaks with major constituents were camphor, trichosenic acid and guanidine. Our current study demonstrates that fruit extracts of R. stricta are cytotoxic toward breast cancer cell lines through apoptotic mechanisms.

Effects of Hexane Root Extract of Ferula hermonis Boiss. on Human Breast and Colon Cancer Cells: An In Vitro and In Vivo Study.

Breast and colon cancers are leading causes of cancer-related deaths globally. Plants are a potential source of natural products that may be used for the treatment of cancer. Ferula hermonis (FH) is reported to have diverse therapeutic effects. However, there are few reports on the in vitro anticancer potential of FH extract. Our results showed that the Ferula hermonis root hexane extract (FHRH) can induce dose-dependent cytotoxic effects in breast and colon cancer cells with MTT IC50 values of 18.2 and 25 µg/ml, respectively. The FHRH extract induced apoptosis in both breast and colon cancer cells; this was confirmed by light and nuclear staining, q-PCR, and caspase 3/7 activation. This study also demonstrated the antitumor activity of FHRH in 9,10-dimethylbenz[α]anthracene DMBA-induced rodent mammary tumor model. The GC/MS analysis revealed the presence of 3,5-Dimethylbenzenemethanol, Alpha-Bisabolol, Alpha-pinene, Beta-pinene, and Baccatin III that have various pharmacological potentials. Overall, the present study suggests that FHRH extract possesses anticancer potential which is mediated through apoptotic effects in MDA-MB-231 and LoVo cells. The present study also considered a basis for further investigations into the potential use of FHRH extract as an anticancer therapy for breast and colon cancers.

The histological spectrum of tubulo-reticular inclusion positive renal biopsies: a tertiary hospital experience and review of the literature.

AIM: To identify the underlying diseases with TRI-positive kidney biopsies, and describe the histological pattern and spectrum of TRI-positive kidney biopsies. METHODS: A retrospective analysis of all patients' chart that underwent renal biopsy at King Saud University Medical City between 2012 and 2017 was done. Kidney biopsies that indicated a positive result for tubuloreticular inclusions (TRI's) on electron microscopy were reviewed and the underlying disease and histological pattern was extracted. RESULTS: Of 1,473 native kidney biopsies reviewed, 96 (6.5%) were TRI-positive. Of the 96 TRI-positive kidney biopsies, 87 (90.6%) were TRI-positive lupus nephritis (LN); of which 10 (11.5%) were Class V, 49 (56.3%) were active LN, and 28 (32.2%) were inactive LN. The underlying diseases of the nine non-LN TRI-positive cases included diabetic nephropathy, connective tissue disorders, immune complex mediated Glomerulonephritis (GN), acute thrombotic microangiopathy, rhabdomyolysis, and Wegener's disease. CONCLUSION: LN is a very common finding in TRI-positive kidney biopsies. Active LN and chronic LN are the more common classes of TRI-positive LN kidney biopsies, than pure membranous (Class V) LN. TRI positive kidney biopsies without LN are commonly found in diabetic nephropathy, connective tissue disorders and immune mediated GN's. This study highlights this finding in our patients cohort in opposition to what has been reported in the literature.

Histopathological Spectrum and Short-Term Outcome of Treatment with Cyclophosphamide in Relapsing Steroid-Sensitive Nephrotic Syndrome.

OBJECTIVE: To determine the short-term outcome of cyclophosphamide (CPO) course in children with relapsing steroid sensitive nephrotic syndrome (SSNS) with different histopathological lesions. STUDY DESIGN: Descriptive, observational study. PLACE AND DURATION OF STUDY: Pediatric Nephrology Department, Sindh Institute of Urology and Transplantation, Karachi, from January 2012 to December 2014. METHODOLOGY: All children with relapsing steroid-sensitive nephrotic syndrome, who underwent renal biopsy and received cyclophosphamide therapy, were included and followed up for 2 years. Histopathological features in renal biopsy, duration of treatment, duration of complete remission and complication frequency was noted. RESULTS: Of the total 74 patients, 47 (63.5%) were males and 27 (36.5%) females. Median age with Interquartile range (IQR) at presentation was 5 years (4-7 years). Minimal change disease (MCD) was the most common histopathological diagnosis (n=54, 73%) followed by focal segmental glomerulosclerosis (FSGS) (n=13, 17.5%), mesangioproliferative glomerulonephritis(MesPGN) (n=6, 8.1%), IgA nephropathy (n=1, 1.4%). The median number of glomeruli included in each biopsy sample was 15. The median duration of treatment with CPO was 11 weeks (9 to 13 weeks), whereas the median duration of complete remission post-therapy was 13 months (7-23 months). A median timeframe of 17 months (13-24.2 months) lapsed between establishing the diagnosis of NS and initiating CPO treatment. Leucopenia was noted in six (8.1%) patients. CONCLUSION: The short-term outcome of relapsing SSNS can be improved with CPO and steroids, with minimum short-term side effects.

Bilateral congenital entropion with cutis laxa.

Cutis laxa is a rare connective tissue disorder characterized by redundant and pendulous skin due to a defect in the elastic fiber network. Two cases of entropion associated with cutis laxa have been reported, although entropion was due to elongation of the anterior lamella or horizontal lid laxity. Thorough systemic and ophthalmic evaluations were performed, as well as chart review for the perinatal period. Surgical correction of entropion through posterior tarsotomy was done. An infant boy with dysmorphic features and furrowing of the skin of the entire body without hyperelasticity, which is typical for cutis laxa, presented with bilateral congenital entropion. We report here for the first time a different etiology of congenital entropion with cutis laxa: the eyelashes were abnormally directed due to the unusual location of their roots, which were embedded within the tarsus. Moreover, this is the only case of cutis laxa with congenital entropion involving both upper and lower eyelids. Congenital entropion can be associated with cutis laxa. Although elongation of the anterior lamella and horizontal lid laxity predispose to such an entropion, abnormal location of the roots of the eyelashes might be encountered and marginal eyelid rotation surgery is indicated.

Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats.

Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.

Ultrastructural alterations in renal tissues of rabbits induced by diclofenac sodium (Voltaren).

OBJECTIVE: Although diclofenac sodium (Voltaren) is one of the most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) worldwide for the treatment of inflammation and pain; data on the ultrastructural alterations in renal tissues due to its chronic exposure are limited. Therefore, the present study was designed to identify the ultrastructural renal alterations induced by diclofenac sodium. METHODS: The experiment was conducted at the animal house of the Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia during the period from April 2003 to June 2003. A total of 30 male rabbits were exposed to intraperitoneal injection with a daily dose of diclofenac sodium (1.5 mg/kg body weight) for 70 days to investigate the resultant ultrastructural alterations in renal tissues. RESULTS: In comparison with the respective control rabbits, chronic exposure to therapeutic doses of diclofenac sodium produced significant ultrastructural renal alterations, which involved swelling and cristolysis of the mitochondria, marked dilatation of the endoplasmic reticulum, detachment of ribosomes, increased lysosomal structures, nuclear chromatin condensation in the tubular cells, thickening of the glomerular basement membranes, distention of glomerular capillaries, which showed lodgment of neutrophils, mesangial and endothelial cell proliferation in the glomeruli, swelling and fusion of the glomerular podocytes foot processes with focal obliteration of the filtration slits. CONCLUSION: The obtained results indicate that chronic exposure to diclofenac sodium produces significant ultrastructural alterations in renal tissues.