Genotoxic and histopathological alterations in rats exposed to herbal liquors

The increase in consumption of herbal liquors in Nigeria is a cause for alarm. These are consumed with the mis-conception that they are without toxic effects. The aim of this study is to investigate the genotoxic and histopathological alterations in rats exposed to herbal liquors. Female rats were exposed to herbal liquors for 6 weeks. The histopathological and genotoxic evaluation were done to assess extent of damage. Pathological examination revealed incidences of aggregates chronic inflammatory cell infiltrates in the heart of Jedi treated group while the heart of the other groups had no abnormalities. The histologic sections of the kidney tissue revealed congested vessels while the lung showed reduction in air filled alveolar spaces with infiltration of alveoli and interstitium by aggregates of inflammatory cells indnadicating moderate to severe pulmonary inflammation. Histologic sections of lung tissue in rats treated with herbal liquors reveals congestion of pulmonary vessels and interstitial hemorrhages. Genotoxic evaluation of rat lymphocytes exposed to herbal liquors via comet assay shows that rats administered with the different herbal liquors developed significant (p < 0.05) as revealed in the % DNA in tail, % DNA in head, olive moment, tail length and tail moment which indicates the presence of DNA strand breaks and a marker for oxidative DNA damage. This result reveals that herbal liquors contain substances that produce reactive oxygen species that have pathological effect on certain organs as well as inducing DNA strand breaks that could compromise the integrity of the DNA which can lead to mutation.

An Immuno-Histochemical Assessment of Ki67, P53 Over-Expression in Helicobacter Pylori Positive Gastritis.

Background and Objective: Helicobacter pylori infection of the stomach is a common disease and the resulting changes from it are numerous and deserve to be in the focus of researchers' attention. The aim of this study is to assess the expression of mutant P53 protein and Ki-67 markers in patients with gastritis secondary to Helicobacter pylori.Methods: Thirty samples with positive Helicobacter pylori gastritis were included in a retrospective study in Mosul / Iraq. The histological parameters were assessed using the Sydney system, then the expression of Ki67 and P53 expression were studied by immunohistochemical methods. The significance level was appointed at (0.05).Results: Ki67 and P53 expression were found in 83.3% of the total cases. The study results show that 92% of positive Ki67, P53 cases had chronic inflammatory cell infiltration, polymorph nuclear cells infiltration, and atrophy. Whereas 96% of positive Ki67 cases had no metaplasia, 92% of the positive P53 cases had no metaplasia. The results also showed that only 16% of the positive Ki67 cases had dysplastic changes, and 24 % of the positive cases of P53 cases were showed dysplasia. moreover, whenever P53 was negative; there is neither metaplasia nor dysplasia in the tissue, this does not apply to Ki67 negative cases.Conclusions: Ki67, P53 expressions increase with chronicity of Helicobacter pylori-positive gastritis, P53 expression is amplified when atrophy is present in these samples

Pulmonary Involvement in Neonatal Lupus from Clinical Diagnoses to Autopsy Findings: A Case Report

Background: Neonatal lupus erythematosus (NLE) is an uncommon immunemediated disease caused by the transplacental passage of maternal autoantibodies. In this paper, we described a case of a newborn with NLE involving lung damage from clinical diagnoses to autopsy findings. Case presentation: The mother had no history of immune system disease; however, the test for antinuclear antibodies was positive. A boy was delivered spontaneously at 36+2 weeks’ gestation without asphyxia (birth weight: 1.21 kg, length: 38 cm, head circumference: 26 cm). Soon after birth, intermittent shortness of breath occurred, followed by cyanosis and severe hypoxemia. Blood tests suggested that the infant was positive for anti-nuclear antibodies. Although multiple respiratory support methods were used, death could not be avoided and occurred at 6.5 days due to cardiopulmonary failure. The results of the autopsy revealed diffuse interstitial inflammation and interstitial fibrosis in both lungs, manifesting as telangiectasia, hyperemia, alveolar cavity dilatation and fusion, and obvious interstitial widening with chronic inflammatory cell infiltration. The newborn was finally diagnosed with nonspecific interstitial pneumonia with fibrosis caused by congenital systemic lupus erythematosus. Conclusions: Pulmonary involvement with NLE is a diagnostic challenge at present. Close attention should be given to newborns whose mothers have systemic lupus erythematosus.

Primary Abdominal Cocoon with Right Intra-Abdominal Cryptorchidism: A Case Report

Background: Primary abdominal cocoon is a special peritoneal disease and easily cause misdiagnosis and mistreatment. Few cases have been reported primary abdominal cocoon with intra-abdominal cryptorchidism in the literature.Case presentation: We admitted one case of a 41-year-old male patient with primary abdominal cocoon and right intra-abdominal cryptorchidism. The main symptom of this patient was intermittent abdominal pain for more than one month, preoperative CT results showed that part of the small intestine folded into a mass, which was suspected of abdominal cocoon. Part of the small intestine was wrapped by fibrous membrane and the right testicle were observed in the abdominal cavity during the operation. Intestinal adhesion release and right cryptorchidectomy were performed successfully. Pathological results revealed that the membranous material was fibrous connective tissue with chronic inflammatory cell infiltration and no spermatogenic cells and sperm were observed in the seminiferous tubules of the testicular tissue. Conclusion: This article reports one case of primary abdominal cocoon with right intra-abdominal cryptorchidism. Primary abdominal cocoon lacks specific clinical manifestations, part of patients may have cryptorchidism and the diagnosis is difficult. We should improve the understanding of primary abdominal cocoon to better save the life of patient.

P395 Impact of mirikizumab therapy on histologic measures of intestinal inflammation in a Phase 2 study of patients with moderately to severely active Crohn’s disease

Background Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02891226) in patients with Crohn’s disease (CD). The histologic results at Week (W)12 induction and W52 maintenance are presented here. Methods Patients were randomized 2:1:1:2 across 4 treatment arms (PBO, 200, 600, 1000mg miri) administered intravenously (IV) every four weeks (Q4W) at Weeks 0, 4, and 8. Patients who received miri and achieved ≥1 point improvement from baseline (BL) at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to continue their IV dose assignment Q4W (IV/IV) or to 300mg miri SC Q4W (IV/SC); maintenance IV arms were pooled for analysis. W12 non-improvers and all induction PBO patients received 1000mg miri Q4W from W12 through W52. Biopsies from terminal ileum and 4 colonic segments (ascending, transverse, descending, rectum) were obtained during endoscopy at W0, 12 and 52 and scored blind to treatment and response status. Ileum and colon scores were reported separately. Colon scores were derived from the sum of the 4 colonic segments, and total intestine scores from the 4 colonic segments plus ileum. Endpoints were defined post-hoc but prior to performing the analyses and only included patients with active histologic disease at BL (see Table). Histologic response was defined as: a) absence of neutrophils in lamina epithelialis, and absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or GHAS ≥50% from BL. Histologic remission was defined as absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Deep histologic remission was defined as histologic remission combined with absence of chronic inflammatory cell infiltration of the lamina propria. For assessment of total intestine inflammation, the criteria for response, remission or deep remission must have been met in all 5 bowel segments. Results At W12, histologic response and remission were significantly higher in all segments of the 1000mg group versus PBO (response: ileum p&lt;0.01, total intestine p&lt;0.01, colon p&lt;0.05; remission: ileum p&lt;0.05, colon p&lt;0.05, total intestine p&lt;0.01). Among the W12 improvers, both histologic response and histologic remission at W52 were similar in ileum and colon in the IV/IV group, but lower in ileum than colon in the IV/SC group. All but 2 patients with remission at W52 were in deep histologic remission. Conclusion Patients treated with miri achieved and sustained histologic response and remission over 52 weeks of treatment. Among patients with W52 histologic remission, all but 2 patients achieved deep remission.

Differentiating Recurrent Thyroiditis From Graves’ Disease on a Background of Lithium Use

A 26-year-old female presented with severe thyrotoxic symptoms 4 months post-partum following an uncomplicated pregnancy; investigations showed a FT4 39.4 pmol/L (n 12 – 22 pmol/L), FT3 8 pmol/L (n 3.1 – 6.8 pmol/L), FT4:FT3 ratio 4.9, TSH &lt;0.02 mU/L (n 0.27 – 4.2 mU/L), TSH receptor antibody (TRAb) &lt; 0.9 IU/L (n &lt; 0.9 IU/L) with normal blood flow on ultrasound doppler and a low (0.2%) Tc99 uptake isotope scan suggesting thyroiditis. 2 years previously she had an episode of thyroiditis (investigations showed FT4 31.2 pmol/L, FT3 7 pmol/L, FT4:FT3 ratio 4.4, TSH &lt;0.02 mU/L and imaging showed low (0.4%) Tc99 uptake) when on lithium 1gm/day for more than a year to treat bipolar disorder. On recurrence, despite compliant treatment with Propranolol and Prednisolone 30mg once daily, thyroid function deteriorated and 2 months later repeat thyroid function testing showed a FT4 &gt; 100 pmol/L, FT3 30.2 pmol/L, FT4:FT3 ratio 3.3 and TSH &lt; 0.02 mU/L. A repeat Tc99 uptake scan showed increased uptake at 13% and ultrasound showed a very vascular bulky thyroid gland. These investigations were suggestive of either a rebound hyperthyroidism (post-thyroiditis) or Graves’ disease. At this stage, TRAb titers were repeated and were now elevated at 4.5 IU/L therefore carbimazole 40mg daily was started. Due to the severity of symptoms, she underwent urgent thyroidectomy. Histopathology showed features of diffuse hyperplasia of the thyroid gland with variably sized follicles lined by cuboidal epithelial cells and a mild patchy chronic inflammatory cell infiltrate in the stroma. Post thyroidectomy she is stable on L-thyroxine therapy. Points for discussion: 1. Lithium is typically used as a mood stabilizer and as thyroid dysfunction is known to exacerbate mood disturbances it is vital that patients are appropriately screened, monitored and treatment is commenced promptly for thyroid disease. 2. Lithium can increase clinical manifestations of thyroid autoimmunity and may influence thyrotoxicosis either due to thyroiditis or Graves’ disease. Differentiating these etiologies is important from the treatment perspective. 3. FT4:FT3 ratios, TSH receptor antibodies, Tc99 uptake scans and ultrasound doppler of the thyroid will assist in diagnostic accuracy. However, in certain rare circumstances, during the recovery phase of thyroiditis, the Tc99 scan can demonstrate diffusely increased activity, which is representative of a rebound phenomenon thus posing a diagnostic dilemma. 4. Finally, TRAb titers may help differentiate the above, but sometimes may change from undetectable to high suggesting changes in thyroid autoimmunity.

Renal injury following long-term exposure to carbon disulfide: analysis of a case series

Background To investigate the clinicopathological characteristics of renal damage caused by long-term exposure to carbon disulfide (CS2) in nine patients. Methods All the patients underwent ultrasound-guided renal biopsy. All specimens were examined by light microscopy and immunohistochemistry (IHC). Samples form one patient were further analyzed using transmission electron microscopy. Results Similar pathological changes were observed in all patients, but the degrees of lesions were different. All cases had moderate to severe nodular mesangial hyperplasia; among these, type “Kimme1stie1-Wi1son” (K-W nodule for short) was observed in four cases, type “K - W nodule” refer to nodular hyperplasia of mesangial membrane like letter K or W. four cases had proliferative extracapillary glomerulonephritis (GN), while there were no concomitant changes in one patient. Besides, six cases had diffuse basement membrane thickening, focal segmental sclerosis or bulbar sclerosis; two cases had diffuse glomerular sclerosis, and one case had focal segmental capillary hyperplasia. Moreover, all patients had renal tubular atrophy/interstitial fibrosis with less to moderate chronic inflammatory cell infiltration, as well as renal arteriosclerosis. IHC showed that the depositions of IgA, IgM, C3d, C4d, C1q and Fib were not specific; while IgG, type III collagen, Fibronectin, Amyloid A, Igκ, Igλ, HBsAg and HBcAg were all negative. Conclusion Diffuse nodular mesangial hyperplasia/sclerosing glomerular nephropathy is characterized by nodular mesangial hyperplasia with type “K-W nodules” formation, which we speculate is a special pathological manifestation of renal damage caused by carbon disulfide (CS2).

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions.

Xanthogranulomatous Oophritis masquerading as ovarian neoplasm: a case report

Xanthogranulomatous inflammation is a special form of chronic inflammation that is destroying normal tissue of affected organs which are replaced by chronic inflammatory cell infiltrate admixed with foci or sheets of foam cells, fibroplasia, chronic inflammatory cell infiltrate and vascular proliferation. Only a few cases of xanthogranulomatous oophoritis have been reported.We report a case of 35 year old female who presented with lower abdominal pain and polymennorhea.A total hysterectomy with bilateral salpingoopherectomy was performed on the suspicion of an ovarian neoplasm.

Tumefactive Multiple Sclerosis Clinically Mimicking Acute Stroke and Lesional Migration Along the Biopsy Tract: A Case Report

Tumefactive multiple sclerosis is a form of demyelinating disease which patient can present with acute stroke. We reported a case of a 49-year-old woman with well controlled hypertension, who presented with right hemiplegia 15 hours prior to admission. The initial diagnosis of acute stroke was made. Emergency computed tomography showed hypodense lesion at the left lentiform nucleus and posterior limb of the left internal capsule. The magnetic resonance imaging (MRI) study showed hyperintense FLAIR lesion in the left lentiform nucleus, left internal capsule, left thalamus, and periventricular area of the left frontoparietal region, some areas of restricted diffusion and inhomogeneous enhancement. The MR spectroscopy (MRS) of the lesion showed increased choline peak, decreased creatine and NAA peaks, and maximal choline to creatine ratio 2.25. Her symptoms deteriorated with progressive headache and motor aphasia. The follow up MRI showed extension of the inhomogeneous enhancing lesion along the biopsy tract at the left frontal lobe with the enhancing and MR spectra pattern similar to the lesion. The craniotomy with left frontal lesion excision included the mass and the biopsy tract was done. The lesion showed acute and chronic inflammatory cell infiltration with macrophages, necrotic tissue and reactive gliosis. The further pathological worked up demonstrated foci of demyelination with relative axonal preservation, numerous CD68+ macrophages with intracyto-plasmic Luxol fast blue(+) myelin debris. Perivascular and parenchymal CD3+ T-cells were identified, especially in demyelinating foci. These findings supported the diagnosis of tumefactive multiple sclerosis. Her conditions were improved after treating with pulse methylprednisolone and intravenous immunoglobulin (IVIG). Follow up MRI study 4 months after treatment revealed almost resolution of the preexisting inhomogeneous enhancing lesion.