Relation between Serological Findings and Expression of IL-1ß and IL-6 genes in Patients Infected with Mycobacterium Tuberculosis in Iraq.

Mycobacterium Tuberculosis (TB) is one of the serious bacterial infections that cause diseases and may lead to death. In this study, 178 individuals were examined for TB infection at Baghdad TB center during the period from 15th January to 1st October 2021. Out of 178 participants, 73 were shown to be positive for TB infection, while 105 showed negative results. According to the results, there was no significant variation between infected males and females with TB in comparison to the control group (P>0.05). The results showed that the mean age of the patients for both males and females was in the range of 2-65 years. Additionally, there were significant differences in patients with TB compared to the control group in terms of the weight loss of 8.82 ± 6.75 Kg, red blood cell (RBC) count (3.43 ± 0.56) × 106/µl, white blood cell (WBC) count (3.12 ± 1.57) × 106/µl, platelet count (1.03 ± 0.56) × 106/µl, and hemoglobin level (6.66 ± 1.34) g/dl. A total of 30 TB patients and 50 normal individuals were genotyped to detect the IL-1ß rs 114534 gene. The polymerase chain reaction (PCR) was used for exon amplification in region 5 of the ILB1 gene in the TB patients by using specific primers. The finding showed that there was an amplified product of 249bp located in chromosome 2q13-14. A total of 30 TB patients and 50 normal individuals were also genotyped to detect the IL-6 rs 1800795 gene. The PCR was used for amplification of the IL-6 gene in TB patients by using specific primers. The finding showed that there was an amplified product of 431 bp located in chromosome 7p15-p2. The expression of the ILB1 gene was investigated in TB patients and healthy controls by using qPT-PCR. Results showed that there was a high Ct value for patients and controls with a high Ct value of templates, preoperational to the total ribonucleic acid (RNA) concentration and gene expression. The expression of the IL-6 gene was investigated in TB patients and healthy controls by using qPT-PCR. Our findings revealed a high Ct value for patients and controls with a high Ct value of templates, preoperational to the total RNA concentration and gene expression.

Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer--a Case-Control Study in Jordan.

BACKGROUND: Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS: The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS: Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.

[Diagnostic modalities of visceral metastases during follow-up of patients with stage I-II melanoma]. / Malades suivis pour mélanome de stade I-II: modalités diagnostiques des métastases viscérales.

INTRODUCTION: Although not recommended in France at the consensus conference of 1994, routine monitoring of patients with stage I melanoma using imaging techniques is commonly carried out. The aim of this retrospective regional study was to define methods for diagnosing transition to the metastatic stage of melanoma. PATIENTS AND METHODS: This was a retrospective study based on questionnaires among dermatologists in the Champagne-Ardenne and southern Aisne regions of France. For each patient with stage IV melanoma between 1987 and 2002, data were collected concerning the primary melanoma (date of diagnosis, clinical picture, histopathologic features), stage of melanoma prior to diagnosis of metastatic melanoma and characteristics of the metastases (date, number, type, site and modern discovery: clinical signs or routine imaging). RESULTS: One hundred and eight patients (63 men and 45 women; mean age: 59 years) were included in the study. The predominant site of the primary melanoma was the trunk for men (n=31) and the lower limbs for women (n=16) and the mean Breslow index was 4.31 mm (SD=4.22), with histologic ulceration being present in 40% of cases. The mean time to transition to stage IV after discovery of the primary tumour was 2.8 years (SD=2.95). The modes of discovery of metastases comprised clinical examination (functional signs or physical examination) in 58 cases and routine imaging in 50 cases, with no significant differences based on whether patients were initially in stage I-II or in stage III. DISCUSSION: This study shows that over half of patients progressing to stage IV melanoma had a suspicious sign or clinical symptom, once again highlighting the importance of clinical monitoring. In contrast, many organ metastases, particularly pulmonary, were discovered by routine imaging examinations carried out as part of patient follow-up, although this is not currently recommended practice in France. CONCLUSION: The role of powerful imaging examinations such as scans, with constantly improving resolution, still remains to be defined in the follow-up of patients with stage I-II melanoma, and further prospective studies are thus required.

Nickel-elicited systemic contact dermatitis from a peripheral intravenous catheter.

Nickel-elicited systemic contact dermatitis is a well-known entity, although it is far less common than allergic contact dermatitis. In most of the cases, the main way of nickel administration is oral. Clinical manifestations are miscellaneous including pompholyx, diffuse exanthema, flexural dermatitis or baboon syndrome. Systemic nickel dermatitis induced by venous catheters is very uncommon, but it is probably underdiagnosed. We report here 2 patients with diffuse recurrent maculopapular rash corresponding to nickel-elicited systemic contact dermatitis. They were both perfused during the last episode with the assistance of a peripheral polyurethane venous catheter during or just before the cutaneous eruption. At the base of the catheter, there was a small metallic eyelet on which dimethylglyoxime test was positive, indicating a release of nickel. Then, we measured nickel release in normal use conditions and found high nickel levels, although the manufacturer denied that nickel could be released. This diagnosis is important to know because such exanthema often occurred during postoperative or postpartum period. Its frequency is probably underestimated because it is often considered as a cutaneous drug reaction. To our knowledge, only 2 cases have been reported in the literature.

N-nitrosodimethylamine: a disinfectant byproduct and its occurrence in wastewater.

This paper will provide wastewater treatment utility professionals with a comprehensive synthesis of information pertinent to N-nitrosodimethylamine (NDMA) so that plant operators can make informed and cost-effective decisions regarding appropriate management techniques. A suspect disinfection byproduct, NDMA is a potential carcinogen and is presently under scrutiny from the U.S. Environmental Protection Agency because it poses a threat to groundwaters from reclaimed wastewaters. Recognizing that the current state of knowledge pertaining to the occurrence and treatment of NDMA from wastewater treatment is in its infancy, the information presented in this paper is timely and will help utility professionals develop confidence toward controlling NDMA during wastewater treatment. Given the increased probability of the formation of NDMA using current wastewater treatment technologies and also in the complex matrices of the wastewaters subjected to UV treatment, the investigation of occurrence pathways and means of suppression of NDMA formation before and after treatment needs to be investigated. This paper also summarizes strategies to minimize exposure such as modifying treatment or instituting waste and agricultural management practices that minimize inorganic and organic nitrogen discharges to wastewaters.

Drugs from the sea: conotoxins as drug leads for neuropathic pain and other neurological conditions.

The oceans are a source of a large group of structurally unique natural products that are mainly found in invertebrates such as sponges, tunicates, bryozoans, and molluscs. It is interesting to note that the majority of marine compounds currently in clinical trials or under preclinical evaluation are produced by these species rather than as secondary metabolites by marine algae. Through the combined efforts of marine natural products chemists and pharmacologists a number of promising compounds have been identified that are either already at advanced stages of clinical trials such as the new anti-cancer drug marine alkaloid ecteinascidin 743, or have been selected as promising candidates for extended preclinical evaluation. This is the case for conotoxins, (Table 1) where a number of conopeptides are currently being developed as analgesics for the treatment of neuropathic pain.

Endothelin and free radicals modulate microvascular responses in streptozotocin-induced diabetic rats.

The quantitative contribution of endothelin and free radicals in modulating peripheral endothelial and smooth muscle-dependent vascular responses in 4 weeks streptozotocin-induced diabetic rats was investigated. Skin blood flow was monitored in base of blisters raised on the hind footpad. Smooth muscle-dependent vasodilation was tested using sodium nitroprusside (SNP). Endothelial-mediated inflammatory responses were induced via either electrical stimulation (ES) of the sciatic nerve or substance P (SP) perfusion over the blister base. Role of endothelin and free radicals was examined using ET-A or ET-B receptor antagonists (BQ-123 or BQ-788) and superoxide anions or hydroxyl radicals scavengers (superoxide dismutase (SOD) or N-acetyl cysteine (NAC)). Diabetic rats showed a significant reduction (75%) in SNP responses that coincided with a 70 and 60% reduction in responses to ES and SP. Their basal plasma extravasation (PE) was significantly higher while PE response to SP was significantly reduced. BQ-788, was more potent than BQ-123, improving responses to ES and SP in diabetic rats by 85%. Likewise, NAC was more potent than SOD normalizing the ES response and improving SP response by 85%. Combined treatment with BQ-123 and SOD normalized all vasodilatation responses in diabetic rats. BQ-123 and BQ-788 were equally potent normalizing the PE responses to SP whereas SOD and NAC had no effect. We conclude that endothelin and free radicals play a role in altering microvascular function in diabetes and that their effect could be reversed early in the disease.

Role of nitric oxide in the actions of substance P and other mediators of inflammation in rat skin microvasculature.

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N(G)-nitro-D-arginine was without effect. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.

Mammalian tachykinins modulate the nicotinic secretory response of cultured bovine adrenal chromaffin cells.

We have studied the modulatory actions of two members of the tachykinin family (neurokinin A and B) on endogenous catecholamine (CA) secretion from cultured adrenal chromaffin cells. Their ability to modulate the nicotinic response was compared to that of substance P (SP). Both neurokinin A and neurokinin B were found to have two distinct actions similar to SP, on nicotine-induced CA release: (1) an inhibitory action at low nicotine concentrations; and (2) a protective action against desensitization by high nicotine concentrations. However, on a molar basis, the efficacy of neurokinin A or B to modulate the nicotinic response (both inhibition or protection) was 30 times less than SP. We have also tested the ability of a SP antagonist (D-Arg1-D-Pro2-D-Trp7,9-Leu11-SP) to antagonize the modulatory actions of SP on the nicotinic response. The results suggest the possibility that SP's actions on the bovine adrenal chromaffin cells might be mediated through two receptor subtypes of two different affinities.

Effect of substance P on nicotine-induced desensitization of cultured bovine adrenal chromaffin cells: possible receptor subtypes.

The neuropeptide substance P (SP) has been reassessed for its ability to modify nicotine-induced catecholamine secretion from cultured bovine, adrenal chromaffin cells. SP exhibited biphasic effects in its actions of inhibiting the nicotinic secretory response and protecting against desensitization. At low concentrations, up to 3 microM, SP partially inhibited or partially protected the nicotine response by 15-20%, and at high concentrations (30 microM), SP markedly inhibited or markedly protected the nicotinic response by 80 or 92%, respectively. The SP antagonist (D-Arg1-D-Pro2-D-Trp7,9-Leu11-SP) completely blocked both effects produced by low concentrations of SP, but not those produced by high concentrations. It is concluded that SP is more potent at protecting against desensitization than at inhibiting the nicotinic response and that SP might modulate CA release through activation of two receptor subtypes.

VIP modulates substance P-induced plasma extravasation in vivo.

Substance P (SP), a putative mediator of neurogenic inflammation, has previously been shown to induce plasma extravasation when exogenously perfused over a blister base induced on the rat hind foot pad. Using the same animal model, we have studied the role of vasoactive intestinal polypeptide (VIP), one of the neuromodulators in primary afferent neurons, on SP-induced plasma extravasation. At all concentrations tested (2.5, 5 and 10 microM), VIP did not cause plasma extravasation by itself, however, it increased that due to 1 microM SP, in a dose-related manner. We have also studied the effect of VIP on the local blood flow in the blister base using a laser doppler-flowmeter. VIP was also found to increase the local blood flow in a dose-dependent manner. The present results provide evidence for the first time in vivo of a role for VIP in modulating a neurogenic inflammatory response induced by SP. The mechanism underlying this action is probably related to the vasodilator activity of VIP.