Background: Latent toxoplasmosis always has the risk of reactivation leading to significant sequelae. The available medications, for chronic toxoplasmosis, are awfully limited by resistance of Toxoplasma cysts. Therefore, there is a growing necessity for novel therapeutic approaches. Agents increasing cAMP levels and downregulating proinflammatory cytokine could inhibit Toxoplasma conversion to the bradyzoite stage. This study explores a potential immunomodulatory effect of rolipram, a PDE4 inhibitor, on the course of experimental toxoplasmosis and links this role to deterrence of the resistant chronic phase of the disease. Materials and methods: Mice infected with low pathogenic strain of Toxoplasma gondii were treated with rolipram for three weeks. The effect of rolipram was evaluated through tissue injury scoring, brain cyst count, specific IgG titers as well as TNF-α, IFN-γ and IL-12 assays. Results: Rolipram was partially able to prevent the progression to chronic toxoplasmosis. Toxoplasma brain cyst burden showed a 74% reduction while Toxoplasma-induced inflammatory foci per liver area and nucleated cells per inflammatory focus were significantly reduced: 57.14% and 61.3% respectively. Significant reduction of TNF-α (84.6%), IFN-γ (76.7%) and IL-12 (71%) levels was demonstrated along with significant inhibition of anti-Toxoplasma antibody response. Conclusion: Rolipram efficiently modulated the Toxoplasma-induced immunological changes with a consequent remission of chronic toxoplasmosis. This study is the first to report the utilization of PDE4 inhibitors as possible immune modulators of chronic phase of Toxoplasma infection.

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Background: Cordylobia anthropophaga, is responsible for nodular cutaneous myiasis in sub-Saharan Africa. The fly has long been limited to tropical Africa except for Asir Province, Saudi Arabia. Al Baha Province; north of Asir has an ecological pattern close to that dominant in subtropical Africa. The Southern parts of Saudi Arabia, including Al Baha, are considered part of the Afro-tropical zoogeographical belt where C. anthropophaga is dominant. A case, with cutaneous nodular lesions, was presented to us, where comprehensive investigations were done to establish the diagnosis and to relate it to the known epidemiological background. Materials and methods: A thorough history taking, comprehensive clinical examination and an intensive parasitological examination on a viable larva recovered from the cutaneous lesions, were performed. Taxonomic identification of the larva was done based on various criteria including shape, size, cuticle spine pattern and the posterior spiracles of the recovered larva. Results: We report a case of cutaneous myiasis, caused by Cordylobia anthropophaga, indigenously acquired in Al-Baha. The recovered larva was identified as the third instar of C. anthropophaga. With no history of travel to Africa or to Asir, along with a comprehensive epidemiological assessment, an autochthonous pattern of transmission was confirmed. Conclusion: We present a new focus of autochthonous transmission of C. anthropophaga in Saudi Arabia suggesting a need for an epidemiological reassessment. We also propose considering Cordylobia myiasis as a differential diagnosis in furuncular skin lesions, even in individuals with no history of traveling to Africa.

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Objectives: Renal cell carcinoma (RCC) in which clear cells with papillary architecture are present is a difficult diagnostic challenge. Clear cell RCC, rarely has papillary architecture. Papillary RCC rarely contains clear cells. However, two recently described types; clear cell papillary and Xp11 translocation RCC characteristically feature both papillary and clear cells. Accurate diagnosis has both prognostic and therapeutic implications. This study aims to highlight the helpful features of each of these entities to enable reproducible classification. Methods: Sixty RCC cases with clear cells and papillary architecture were selected and classified according to The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia and graded according to The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma then stained for CK7, carbonic anhydrase IX (CA IX), α-methylacyl-CoA-racemase (AMACR) and TFE-3. Results: The characteristic immunoprofile of Clear RCC is CK7−, AMACR−, CA IX+ and TFE3−, papillary RCC is CK7+, AMACR+, CAIX− and TFE3−, while for clear cell papillary RCC it is CK7+, AMACR−, CAIX+ and TFE3− and lastly Xp11 translocation RCC is CK7−, AMACR+, CAIX− and TFE3+. Conclusions: Staining for CA IX, CK7, AMACR and TFE3 comprises a concise panel for distinguishing RCC with papillary and clear pattern.

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Background: Colon and colorectal cancer (CRC) research has entered a new era with recent updates of molecular events and prognostic markers. Among other prognostic markers, exaggerated expression of nuclear CCND1 has key role in tumour pathogenesis and metastases of CRC and has also been claimed to predict response to treatment. Objectives: This study was designed to evaluate the prognostic and predictive value of CCND1 in CRC and the correlation of CCND1 expression with the different clinicopathological parameters. Methods: Paraffin blocks from 117 primary CRC were retrieved from the archives of the Department of Pathology at King Abdulaziz University. Tissue microarrays were designed and constructed. The immunostaining of CCND1 was performed and analysed. Results: There were more cases with low nuclear immunoexpression of CCND1 in both primary tumours and nodal metastasis (p <0.001). Cyclin D1 did not show association with clinicopathological features except with lymphovascular invasion. Low nuclear immunoexpression of CCND1 was associated with negative lymphovascular invasion (p = 0.046). There was no statistically significant correlation between CCND1 immunoexpression and survival probability (Log Rank = 2.474, p = 0.116). Conclusion: Our study indicates that CCND1 immunoexpression cannot be used as a predictor of survival in CRC. It also shows no significant correlation with clinicopathological features except with lymphovascular invasion.

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Androgen receptor (AR) and proliferating cell nuclear antigen (PCNA) play a crucial role in development and progression of various prostatic diseases including prostatic carcinoma that is a leading cause of death in males. Previous studies have evaluated the expression pattern of AR and PCNA in prostate epithelial cells using immunohistochemistry (IHC). However, this technique has limited ability to identify their precise subcellular localization. Therefore, the aim of this study was to localize, subcellularly, AR and PCNA in the secretory epithelial cells of rat ventral prostate using post embedding immunogold-electron microscopy. The ventral lobes were dissected from six adult male albino rats after being perfused with paraformaldehyde. Some specimens were immuno-labeled with AR or PCNA and others were processed for immuno-electron microscope of AR and PCNA using 15-nm gold conjugated secondary antibodies. The results showed that, by immunoperoxidase reaction, AR and PCNA were localized diffusely throughout the nuclei of the epithelial cells of prostatic acini without visible cytoplasmic expression. However, the higher resolution immuno-electron microscopy was able to detect AR and PCNA in the nucleus and some cytoplasmic organelles. In conclusion, this study emphasizes the importance of immuno-electron microscopy in precise localization of AR and PCNA at the subcelullar levels in the secretory epithelial cells of the rat prostatic acini. These findings will help to further understand the mechanism of action of these receptors under normal and pathological conditions that could have future clinical application after careful human investigation.

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The noticeable phenomenon of an increased frequency of immune-inflammatory disorders, in the industrialized world, has led to the implication of parasitic infections in the pathophysiology of these diseases. Most of the studies investigated the infection connection to allergy have centered on helminthes. Parasitic helminthes are a group of metazoans that are evolutionary diverse, yet converge to evolve common modes of immunomodulation. Helminth immunoregulation is mainly mediated by a regulatory response including Treg and Breg cells with alternatively-activated macrophages. There is increasing evidence for a causal relationship between helminth infection and allergic hyporesponsiveness, however, conflicting data are still generating. The helminth immunoregulation seems to be species-specific and phase-specific. It depends on the stage of the clinical disease which correlates with a corresponding parasitic stage (egg, larva or mature adult). Here, we review the cellular and molecular mechanisms utilized by helminthes to manipulate the immune system and the consequent bystander immunomodulatory responses toward environmental allergens. We especially focus on parasitic species and molecules involved in the modulation of allergic disorders and summarize the experimental and clinical trials using them as therapeutic agents. We also discuss the potentials and obstacles, for helminthes and/or their derived molecules, to emerge as novel therapeutic modalities.

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This study presents the morphological and physiological characterization of the salivary glands of semi-engorged Amblyomma triste females. Unfed individuals were placed on New Zealand White rabbits for feeding and the females, after 4 days, were collected, dissected and the salivary glands were submitted to the application of histological (hematoxylin–eosin technique) and histochemical tests for the detection of protein (bromophenol blue technique, polysaccharides (periodic acid–Schiff technique), lipid (Nile blue technique) and calcium (von Kossa technique). The histological results show that the glandular tissue is composed by a system of ducts and three types of acini (I, II and III). The acini I are formed by a large central cell surrounded by several smaller agranular peripheral cells. Acini II are formed by cells a, c1, c2, c3 and c5, which are full of secretion granules. Acini III are constituted by cells d, e and f; the former two contain secretion granules, the latter is agranular. The glandular histochemical composition was also verified. Data obtained here will certainly help in the understanding of the cellular morphology and of the general physiology of these organs in this specie, providing important information for the creation of scientific bases which will contribute for the development of more specific and efficient methods of control.

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