CLPB Deficiency Associated Neonatal Cavitating Leukoencephalopathy: A Potential Pathomechanism Underlying Neurologic Disorder.

Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in CLPB (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures. Brain macroscopic examination demonstrates frontal severe periventricular cystic leukoencephalopathy, along with mild ex-vacuo tri-ventricular dilatation. The most striking immunohistopathologic features are striato-thalamic neurodegeneration and deep white matter loss associated with strong reactive astrogliosis. This report supports that CLPB deficiency should be considered among the neurometabolic disorders associated with severe prenatal-onset neurologic impairment that may result from cystic leukoencephalopathy.

A giant gastrointestinal stromal tumor revealed by a life-threatening hematemesis: A case report of a rare entity and a challenging management.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal malignancies in the digestive tract. Despite the stomach being their site of predilection, only a few giant GISTs have been discovered in hypovolemic shock and require urgent surgery. CASE PRESENTATION: A 62-year-old patient was admitted for hematemesis. Initial examination revealed a compensated hemodynamic shock with a mass in the left hemi abdomen of 20 cm without signs of portal hypertension or peritonitis. After resuscitation, an abdominal CT scan was performed, showing an exophytic mass of the gastric antrum without local or distant lymph node involvement. Later, the patient went into hemodynamic shock, requiring vasoactive drugs. An urgent midline laparotomy was performed, revealing a 20-cm gastric GIST in the anterior wall of the antrum. Wedge resection was performed. The anatomopathological report confirmed the diagnosis of gastric GIST with a moderate risk of recurrence. The patient received adjuvant therapy for 3 years. No recurrence was detected. CLINICAL DISCUSSION: Bleeding gastric GISTs revealed by a hypovolemic shock is a rare yet critical scenario. Considering GISTs as an etiology of digestive bleeding in life-threatening cases requires a high index of clinical suspicion. Prompt intervention is vital to control hemostasis and ensure patient stability. CONCLUSION: Open surgery is mandatory for large bleeding GISTs. The surgical approach must be tailored to the tumor's specific location. Diligent execution of the surgical procedure is vital to prevent tumor rupture. Despite their size, these tumors have a favorable prognosis, enhanced by adjuvant therapy for moderate to high recurrence risk.

Sigmoid-rectal intussusception in an elderly patient: A case report of an unusual presentation of intestinal obstruction.

INTRODUCTION: Sigmoid-rectal intussusception or invagination is an infrequently documented condition in the adult population, with only a handful of cases reported in the medical literature. The underlying pathological mechanism involves impaired peristalsis, often attributed to a malignant tumor. CASE PRESENTATION: A 78-year-old patient, with a history of abdominal pain and lower gastrointestinal bleeding, sought care at our emergency department with evident symptoms indicative of large bowel obstruction. Abdominal examination revealed distension and rectal examination found a mass mimicking an internal rectal prolapse. Subsequently, imaging studies confirmed the diagnosis of sigmoid-rectal intussusception. The patient underwent an emergency open sigmoid resection with Hartman's procedure. The postoperative course was uneventful. Anatomopathological analysis revealed the presence of stage I adenocarcinoma. A restoration of digestive continuity was scheduled six months later. One-year follow-up assessments showed no indications of local recurrence or distant metastasis. DISCUSSION: Sigmoid rectal intussusception stands as a unique and infrequently reported medical entity. The absence of distinct clinical symptoms often renders diagnosis a challenging task, with confirmation typically relying on radiological findings. In contrast to the non-surgical approaches employed in pediatric cases, intussusception in adults necessitates surgical intervention due to its predominantly malignant underpinnings. CONCLUSION: While sigmoid-rectal intussusception is an exceedingly rare occurrence, its manifestation with a multitude of non-specific symptoms can complicate clinical recognition. Nevertheless, it should be duly considered as a potential etiological factor in cases of large bowel obstruction, particularly when suggestive signs are found on rectal examination.

Severe Ciliopathy-Like Phenotype in an Infant With a Novel MPDU1 Missense Variant.

Congenital disorders of glycosylation (CDG) are associated with ciliary dysfunction due to altered glycosylation of ciliary glycoproteins. We describe a severe ciliopathy-like phenotype in a female infant associated with a novel homozygous missense variant NM_004870.4(MPDU1):c.503G>A/p.Gly168Glu. Our findings, based on the co-segregation of the variant with the phenotype and in-silico analysis, implicate this MPDU1 missense variant in this disorder. Matched phenotype includes symmetric growth restriction, facial dysmorphism, ichthyosis, hepatomegaly with severe duct plate malformation, renal cortical tubular and glomerular cysts, moderate cerebral tetraventricular dilatation, and severe pontocerebellar hypoplasia. According to this observation, CDG should be included in the workup of infantile ciliopathy-like disorder.

A severe clinicopathologic phenotype of RAF1 Ser257Leu neomutation in a preterm infant without cardiac anomaly.

Phenotype analysis of the Noonan syndrome (NS) related to RAF1 mutations demonstrates that a high proportion of cases exhibit severe lymphatic dysplasia and congenital heart disease, especially hypertrophic cardiomyopathy. Because of the difficulty of fetal phenotypic assessment, the percentage of cases with multisystemic prenatal presentation as well as the phenotypic variability may be underestimated. We describe a 35 weeks male preterm infant presenting with de novo missense mutation NM_002880.4(RAF1):c.770C>T (p.Ser257Leu), whose death occurred following birth. Antenatal ultrasound showed polyhydramnios, severe ascites, and tongue protrusion. Autopsy revealed multiple congenital anomalies including intrauterine growth restriction, hydrops fetalis, characteristic facial dysmorphia, short and webbed neck, hypertrichosis, severe lungs hypoplasia, thymic hyperplasia, hepato-splenomegaly, bilateral mild uretero-hydronephrosis, and mild pontocerebellar hypoplasia. Histology revealed increased hepatic hematopoiesis and iron deposits. This report confirms that NS may be associated with multisystem involvement and provides further evidence for the wide phenotypic variability associated with RAF1 variants.

Alleviated Actions of Plantago albicans Extract on Lead Acetate-Produced Hepatic Damage in Rats Through Antioxidant and Free Radical Scavenging Capacities.

The aim of this study was to explore the possible protective mechanisms and to determine the antioxidant capacity of phenolic compounds extracted from Plantago albicans against lead acetate-induced hepatic injury. High performance liquid chromatography-photo diode array/electrospray ionization-mass spectrometry (HPLC-PDA/ESI-MS) assay was used to identify the P. albicans extract phenolic compounds. Animals received 100 mg of lead acetate/kg of body weight (bw) in the drinking water for a period of 30 days. The other groups of rats were orally administered with silymarin (300 mg/kg bw) or the P. albicans extract at two doses (100 and 300 mg/kg of bw), once daily, by gastric gavage for the same time. The P. albicans exhibited high total phenolic, flavonoid, and anthocyanin contents. The antioxidant in vitro activity demonstrated that the P. albicans exhibits an important effect against deleterious reactive species. The in vivo results showed that P. albicans prevented the lead acetate-induced significant changes on serum and liver lipid levels. In contrast, P. albicans succeeded in improving the biochemical parameters of serum and liver bringing them closer to the normal values of the control group. It also significantly promoted (P < .05) pro-inflammatory cytokines (TNF-α, IL-6, and NF-κB) in the liver of the experimental animals. The evaluated sample with HPLC-PDA/ESI-MS method showed to contain 10 dominant polyphenols, 2 hydroxycinnamic acids (p-coumaric acid and chlorogenic acids), 4 flavones (Apigenin, Luteolin, Cirsiliol, and Luteolin-7-O-rutinoside), and an anthocyanin (cyanidin-3-glucoside). Hence, it can be concluded that P. albicans could be a potent source of health-beneficial phytochemicals providing a novel therapy to protect liver against lead exposure.

Histopathological and Biochemical Effects of Thyme Essential Oil on H2O2 Stress in Heart Tissues.

BACKGROUND: Thymus algeriensis (T. algeriensis) is traditionally used in Tunisia to treat many human diseases. The aim of the present study was to investigate whether terpenes extracted from the aerial parts of T. algeriensis are potent cardioprotective agents for hydrogen peroxide (H2O2)-induced cardiotoxicity in rats. METHOD: Thirty (30) rats were divided into six groups as per the experimental design: control (n = 6); 0.1 mmol/L H2O2 (LD H2O2) (n = 6); 1 mmol/L H2O2 (HD H2O2) (n = 6); oily fraction of T. algeriensis (OFTS) (180 mg/kg b.wt) (n = 6); OFTS + 0.1 mmol/L H2O2 (n = 6); and OFTS + 1 mmol/L H2O2 (n = 6). RESULTS: The H2O2 demonstrated concentration-dependent cardiotoxic effects in vitro. While, exposure of rats to OFTS significantly depleted H2O2-induced protein oxidation and lipid peroxidation, it raised antioxidant defence enzymes, and protected against H2O2-induced histopathological alterations. The antioxidant potential of the thyme essence was assessed by both enzymatic and non-enzymatic antioxidants. CONCLUSION: In conclusion, OFTS may be a potential compound for the therapy of oxidative stress-induced heart disease.

Fetal mediastinal teratoma: Misinterpretation as congenital cystic lesions of the lung on prenatal ultrasound.

Congenital mediastinal teratoma can lead to development of hydrops fetalis and may be misinterpreted on ultrasound. In this case report, ultrasound revealed severe fetoplacental hydrops, moderate posthemorrhagic hydrocephalus, and multiple pulmonary cysts suggesting cystic adenomatoid malformation and displacement of the heart to the left side. Autopsy of the hydropic 24-weeks male fetus showed a large cystic-solid mediastinal mass that was consistent with nonmetastatic immature teratoma. It also demonstrated thymic, cardiac and pulmonary hypoplasia, and confirmed the germinal matrix-intraventricular hemorrhage. Accurate prenatal diagnosis of mediastinal teratoma may be achieved by a careful Doppler ultrasound assessment that also allows evaluating the fetal outcome.

Congenital Large Cutaneous Hemangioma with Arteriovenous and Arterioarterial Malformations: A Novel Association.

BACKGROUND: Congenital cutaneous hemangioma is a benign vascular lesion that is a leading cause of severe hemodynamic compromise in a fetus when it is of significant size and especially in association with arteriovenous malformation. CASE REPORT: A large cutaneous hemangioma involving the right arm of a 32-week-old male fetus was complicated by fetal hypotrophy, hydrops fetalis and neonatal death. Axillary arteriovenous fistulas and bilateral arterial carotid-subclavian anastomosis were demonstrated at autopsy. Microscopically, the main tumor was a mixed capillary-cavernous hemangioma with vascular channels lined by CD31-positive and GLUT1/Ki-67-negative endothelial cells. CONCLUSION: Congenital hemangioma can be associated with vascular malformations, and that associations with other vascular malformations may increase the morbidity/mortality.

Hydrogen peroxide-induced oxidative stress, acetylcholinesterase inhibition, and mediated brain injury attenuated by Thymus algeriensis.

The aim of the current study was to evaluate acetylcholinesterase (AChE) inhibition, antioxidant enzyme activities, and malondialdehyde (MDA) levels induced by hydrophobic fractions of Thymus algeriensis (HFTS) growing in Tunisia. The results showed that hydrogen peroxide (H2O2), an oxidative stress inducer, acts by decreasing the body mass and brain mass of rats. Moreover, we found higher MDA levels in the group treated with H2O2 (P < 0.05) and a significantly lower activity of catalase, glutathione peroxidase, glutathione S-transferase, and superoxide dismutase, as well as a reduction in reduced glutathione activity in the brain tissues of H2O2-treated rats when compared with those of the control group (P < 0.05); however, rats that received HFTS with H2O2 experienced a decrease in MDA levels in the brain. In contrast, HFTS demonstrated neuroprotective effects in rat brain. Overall, exposure to HFTS prior to H2O2 induced a marked dose-dependent increase in reactive oxygen species scavenger levels (P < 0.05) accompanied by a statistically significant decrease in MDA levels (P < 0.05) when compared with no exposure. Notably, the activity of AChE was affected by exposure to natural compounds; levels were significantly lower in HFTS-treated rats and in those treated with the combination of HFTS and a low or high dose of H2O2. Furthermore, histopathological analysis showed that brain injuries occurred with high doses of H2O2 administered alone or with a low dose of HFTS, whereas a high dose of essential oil markedly alleviated neurone degeneration. The results suggest that HFTS alleviates neuroinflammation by acting as an AChE inhibitor and attenuates H2O2-induced brain toxicity.

Histopathological indices and inflammatory response in the digestive gland of the mussel Mytilus galloprovincialis as biomarker of immunotoxicity to silver nanoparticles.

BACKGROUND: Histopathological assessments approaches in bivalves have become an important tool in environmental toxicology. This study seeks to develop a quantitative histopathological index (Ih) and inflammation score as biomarkers in the aim to assess the health status of nanoparticles exposed mussels. METHODS: Digestive gland hematoxylin and eosin (H&E) stained sections from Mytilus galloprovincialis were assessed after in vivo exposure (for 3, 6 and 12 h) to silver nanoparticles (Ag-NPs < 50 nm and Ag-NPs < 100 nm) prior and after manipulating the potential uptake pathways (clathrin- and caveolae-mediated endocytosis) using amantadine and nystatin as blockers. Quantitative models evaluate the impacts of nanoparticles size, as well as their uptake routes within different time of exposure on the inflammation intensity, the digestive tubules histomorphometry and the histopathological indices. RESULTS: Silver nanoparticles clearly induced histopathological alterations in digestive gland (maximum inflammation 2.75 with AgNP < 100 nm [p < 0.05]; significant Ih with AgNP < 50 nm and AgNP < 100 nm at different time-points [p < 0.05]). Significant Ih were recorded after uptake routes were blockade: AgNP < 50 nm + nystatin and AgNP < 100 nm + amantadine; [p < 0.05] all time-points. CONCLUSIONS: Histopathological assessments showed to be promising tool in nanotoxicity which seems to depend on nanoparticles size, exposure time and interestingly to uptake routes. It was not clear: is it the length of exposure or the size of particles is more impactful.

Histopathology and analyses of inflammation intensity in the gills of mussels exposed to silver nanoparticles: role of nanoparticle size, exposure time, and uptake pathways.

Environmentally induced perturbation of health parameters lead to morphological changes associated to the inflammatory response. Hematoxyline and eosin (H&E)-stained gill filaments sections were examined for such changes and inflammation intensity was scored according to a quantitative model in order to evaluate the health status of in vivo exposed (for 3, 6, and 12 h) mussels to silver nanoparticles (Ag-NPs <50 nm and Ag-NPs <100 nm) prior and after the inhibition of two potential uptake pathways (clathrin- and caveolae-mediated endocytosis) with the aid of pharmaceutical inhibitors (amantadine and nystatin). The impacts of the nanoparticles (NPs) size, as well as their uptake routes within different time of exposure on the inflammatory response were assessed. The results showed that Ag-NPs clearly induced morphological changes associated to the inflammatory response in gill tissues (Mann-Whitney p values were <.05). It is also clear that the length of the exposure as well as the NP size highly impacted inflammation intensity (highest histopathological indices recorded with Ag-NPs <100 nm). Also, the routes of NPs entry noticed to be major factor underlying inflammatory response (significant inflammation intensity reported with Ag-NPs <50 nm after blockade of uptake routes; p <.05). Throughout, it was concluded that inflammation intensity was related to NPs size and exposure time. Overall, uptake routes are shown to be the major factor underlying nanotoxicity.

Antioxidant Machinery Related to Decreased MDA Generation by Thymus Algeriensis Essential Oil-induced Liver and Kidney Regeneration.

OBJECTIVE: This study was conducted to determine the histopathological and biochemical effects of Thymus algeriensis essential oil (TEO) on hydrogen peroxide (H2O2)-induced oxidative stress in liver and kidney tissues of rats. METHODS: Rats were treated in six groups and were exposed for 2 weeks to low (LD; 100 µmol/L) and high doses (HD; 1 mmol/L) of H2O2 in the presence or absence of TEO (180 mg/kg). Liver and kidney atrophy was measured by using biochemical and histopathological assays. RESULTS: Our study demonstrated that H2O2 induced liver and kidney atrophy, as evidenced by the significant elevation of serum aminotransferase, urea, and creatinine levels compared with those in the control rats. Urea levels were estimated by evaluating the activity of serum urease that hydrolyzes urea into CO2 and ammonia. However, TEO treatment significantly alleviated oxidative stress in the H2O2-induced liver and kidney toxicity model by reducing the levels of malondialdehyde concomitantly with marked elevations in superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, as well as decrease in glutathione activity. CONCLUSION: Our data demonstrated that TEO protected against H2O2 toxicity by decreasing oxidant levels and DNA damage, as well as increasing antioxidant levels, indicating that TEO has a spectrum of antioxidant and DNA-protective properties.

Prevention of H2O2 Induced Oxidative Damages of Rat Testis by Thymus algeriensis.

OBJECTIVE: We evaluate the effects of Thymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats. METHODS: Rats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg). RESULTS: The results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls. The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity and significant increase (P<0.05) in MDA concentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2 generated oxidative stress. These results were confirmed by histological architecture examinations. CONCLUSION: H2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.

Effects of Thymus hirtus sp. algeriensis Boiss. et Reut. (Lamiaceae) essential oil on healing gastric ulcers according to sex.

BACKGROUND: Thymus algeriensis Boiss. et Reut. (Lamiaceae), popularly known as "mougecha" or "mazoukcha" is prolific in Mediterranean regions, mostly in North Africa, and is used in folk medicine to treat of stomach diseases. METHODS: In this study, animals were induced with gastric ulcers using HCl/ethanol (0.3 M HCl/60% ethanol) and treated orally with essential oil of Thymus algeriensis (EOTa) in various doses ranging from 54 mg/kg body weight to 180 mg/kg body weight. RESULT: The dose found to be effective was 180 mg/kg body weight, since this dose brought about a maximum reduction in lesion index in female rats. In gastric tissues, levels of total glutathiones (GSH, GST and GPx) and thiobarbituric acid reactive substances (TBARS) were evaluated. The activities of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured. Histopathological changes were observed using a cross section of gastric tissue. Chemical analysis revealed the presence of 13 components accounting for 77.7% of the essential oil from dried leaves. Oral administration of EOTa (54, 117 and 180 ml/kg) inhibited HCl/ethanol-induced ulcers. Lesion index was significantly reduced in ulcer induced animals treated with EOTa (HCl/ethanol + EOTa) compared to those ulcerated with HCl/ethanol but with no treatment given. Females showed a greater resistance to ulcers and gastric lesions occurred less often than in males. GSH, pH, enzymic antioxidants, and adherent mucus content were all significantly increased. CONCLUSION: From the data presented in this study, it can be concluded that male rats are more sensitive to gastric ulcers induced by HCl/ethanol than females.