Genitourinary Sarcoidosis

Genitourinary involvement of sarcoidosis can mimic many common urologic conditions. Although sarcoidosis is a benign inflammatory condition, it can present much like malignant or infectious conditions; thus, failed diagnosis can lead to unnecessary medications or surgical procedures. In addition, management choices for patients with scrotal findings have important implications for future fertility. Thus, this uncommon condition should be on the differential diagnosis for any urologic patient. The authors report on a patient with a scrotal mass as his presenting symptom of sarcoidosis and review the diagnosis, implications, and management of sarcoidosis involving all potential sites in the urinary tract.Key words: Sarcoidosis, Genitourinary, Scrotal mass, UrologyScrotal masses comprise a wide differential diagnosis. Although the vast majority of isolated epididymal masses are benign, solid testicular masses in adults are generally considered malignant until proven otherwise. Benign sarcoid lesions can occur in the testis, epididymis, or any other scrotal structure. In fact, sarcoidosis can involve many organs of the genitourinary (GU) system, commonly masquerading as other, more common conditions, including malignancy and infection.We present a patient with a scrotal mass as his presenting manifestation of sarcoidosis. This is followed by a concise review of the diagnosis and management of sarcoidosis, and a review of the limited literature available specifically pertaining to sarcoidosis of the GU tract. Finally, we provide initial management recommendations for each GU site of disease.     

Morphine modulates monocyte-macrophage conversion phase

Monocyte migration and their activation into the macrophage phenotype play a role in the modulation of tissue injury. We studied the effect of morphine on the monocyte-macrophage conversion phase (MMCP). Phorbol 12-myristate 13-acetate (PMA) activated THP-1 cells and promoted their adhesion to the substrate. Morphine inhibited PMA-induced MMCP. However, opiate receptor antagonists attenuated this effect of morphine. Interestingly, PMA as well as morphine-stimulated superoxide production by monocytes. Superoxide dismutase (SOD) not only inhibited PMA-mediated MMCP but also attenuated the inhibitory effect of morphine. PMA not only enhanced adhesion of monocytes to a filter but also promoted their migration. These findings suggest that the PMA-induced macrophage phenotype conversion may be accelerating their migration; whereas, morphine may be preventing the migration of monocytes by inhibiting MMCP.     

An efficient synthesis of acyclic N7- and N9-adenine nucleosides via alkylation with secondary carbon electrophiles to introduce versatile functional groups at the C-1 position of acyclic moiety

The introduction of versatile functional groups, allyl and ester, at the C-1 position of the acyclic chain in acyclic adenine nucleosides was achieved for the first time directly by alkylation of adenine and N6-potected adenine. Thus, the C-1'-substituted N9-adenine acyclic nucleoside, adenine-9-yl-pent-4-enoic acid ethyl ester (11), was prepared by direct alkylation of adenine with 2-bromopent-4-enoic acid ethyl ester (6), while the corresponding N7-regioisomer, 2-[6-(dimethylaminomethyleneamino)-purin-7-yl]-pent-4-enoic acid ethyl ester (10), was obtained in one step by the coupling of N, N-dimethyl-N'- (9H-purin-6-yl)-formamidine (9) with 2-bromopent-4-enoic acid ethyl ester (6). The functional groups, ester and allyl, were converted to the desired hydroxymethyl and hydroxyethyl groups, and subsequently to phosphonomethyl derivatives and corresponding pyrophosphorylphosphonates.     

2-Substituted N-aryl piperazines as novel triple reuptake inhibitors for the treatment of depression

Recently a class of compounds known as triple reuptake inhibitors has emerged as a new strategy for the treatment of depression. These compounds work by simultaneously inhibiting the synaptic reuptake of serotonin, norepinephrine and dopamine. In this Letter we describe the optimization of a novel series of 2-substituted N-aryl piperazine based triple reuptake inhibitors.     

Association between -174 G/C promoter polymorphism of the interleukin-6 gene and progression of prostate cancer in North Indian population

The cellular alterations that give rise to cancer initiate changes in cytokine expression. Though IL-6 is known to play a major role in proliferation of tumor cells, IL-4 upregulates androgen receptors and prostate-specific antigen (PSA). The present study was undertaken to evaluate the association of IL-4 and IL-6 gene polymorphisms for the susceptibility to prostate cancer (PCa) risk. Our study included 200 controls and 200 histologically confirmed cases of PCa. Polymorphisms in IL-4 (intron 3, by VNTR analysis) and IL-6 (-174 G/C, by amplification refractory mutation system, i.e., ARMS-PCR) were genotyped in all the subjects. There was no significant association of IL-4 and IL-6 gene polymorphisms with the risk of PCa. Nevertheless, twofold risk with progression to bone metastasis (odds ratio = 2.09; 95% confidence interval = 1.16-3.75; p = 0.014) in PCa patients was observed. No association with other confounding factors such as PSA level, Gleason score, and lifestyle-associated risk factors like tobacco chewing and cigarette smoking was seen. Our study suggests that an IL-6 gene variant may be associated with prostate progression and bone metastasis.     

Synthesis of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives as possible antiviral agents

A number of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives having hydroxymethyl at C-1' position were prepared from the appropriate 6-chloroadenine derivative. The syntheses of the corresponding prodrugs of these compounds are also reported. These compounds showed poor activity against HCV in replicon assay.