Oral Cd Research Articles

Case report: Vedolizumab in Oral Crohn’s disease: the downsides of a gut-specific therapy for a multi-site disease

IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease which can affect any area of the gastrointestinal tract, including oral tissues. The complex nature of this disease demands interdisciplinary management, especially when both intestinal and oral manifestations are present.CaseThis report presents the case of a 28-year-old male patient with oral, ileo-caecal and peri-anal CD managed jointly between Gastroenterology and Oral Medicine. Treatment with vedolizumab, an α4β7 integrin with gut-selective anti-inflammatory activity, resulted in excellent ileo-caecal disease control, but was ineffective in controlling oral manifestations. The absence of MAdCAM-1 expression in oral tissues, necessary for vedolizumab’s mechanism, meant that the drug’s anti-inflammatory effects were limited to the gut. This limitation led to worsening oral symptoms, necessitating concomitant azathioprine therapy to manage oral inflammation.ConclusionMultidisciplinary collaboration is important when managing CD patients with both oral and gut involvement in CD. Clinicians should be aware that vedoluzimab may be beneficial for intestinal CD, but does not target inflammation in oral tissues due to its gut-specific action. Good knowledge of the pharmacology and mechanism of action of drugs prescribed can aid decision making when prescribing for this group of patients and can limit the need for polypharmacy, often associated with an increased adverse effect profile.

Influence of titanium dioxide nanoparticles and/or cadmium chloride oral exposure on testicular morphology, oxidative stress, and apoptosis in rats: Ameliorative role of co-enzyme Q10

Background and objectivesLittle is known about the implications of titanium dioxide nanoparticles (TiO2NPs) and cadmium chloride (Cd) co-exposure on the male reproductive system in mammals. As a result, this study researched the effects of oral TiO2NPs and/or Cd exposure on male reproduction and testicular functions. Additionally, a mitigation trial with co-enzyme Q10 (CoQ10) has also been conducted. MethodsIn a 60-day experiment, seven experimental groups, each containing 10 male Sprague Dawley rats, were orally given distilled water (control), corn oil (vehicle control), CoQ10 (10 mg/kg b.wt), TiO2NPs (50 mg/kg b.wt), Cd (5 mg/kg b.wt), TiO2NPs + Cd, and TiO2NPs + Cd + CoQ10. Then, sperm quality, male sex hormones, oxidative stress indications, Ti and Cd testicular residues, testes and accessory gland architecture, and apoptotic and inflammatory markers in rat testes were assessed. ResultsTiO2NPs and/or Cd exposure negatively impacted body weight, weight gain, testicular weights, semen quality, serum reproductive hormones, oxidative stress parameters, and Caspase-3 and tumor necrosis factor (TNF-α) immunoreactions. Histopathological changes were recorded in testicular, seminal vesicle, and prostatic tissues. Yet, co-administration of CoQ10 with TiO2NPs and Cd substantially mitigated these adverse consequences. The most notable aspect is that it effectively lowered testicular tissue Ti and Cd levels. It also improved oxidant status, hormonal profile, and sperm picture. CoQ10 minimized the testicular damage implied by histological examination. Furthermore, CoQ10 significantly diminished TiO2NPs and Cd-induced Caspase-3 and TNF-α immunoexpression in testicular tissue. ConclusionAs a result, CoQ10 could be utilized as a safe remedy to protect male reproductive physiology from TiO2NPs and Cd damage.

Assessment of serum levels of anti-gliadin (IgA and IgG) antibodies in patients with lichen planus: A pilot study

elevated AGA levels have been reported in several immune-mediated cutaneous conditions even in the absence of gastrointestinal disease clinical manifestations. A gluten-free diet led to improvements in some of these disorders. The link between oral lichen planus (LP) and CD was revealed, but there is currently no information available regarding the association between cutaneous LP and gluten sensitivity. This study aimed to assess the AGA (IgA and IgG) serum levels in LP patients compared to controls and to determine their correlation with LP severity. The study included 20 patients with cutaneous LP and 20 age- and sex-matched controls, both free of CD manifestations. The enzyme-linked immunosorbent assay (ELISA) technique was utilized for the evaluation of AGA (IgA and IgG) serum levels. Hepatitis C virus (HCV) antibodies in LP patients were evaluated qualitatively using a chromatographic immunoassay. In LP patients, AGA (IgA and IgG) serum levels were significantly elevated compared to controls (p = 0.015 and p=0.016, respectively). A significant positive correlation between AGA (IgG) serum levels and the age of patients (p= 0.024), duration of disease (p= 0.02), and LP severity index (p< 0.0001) was found. AGA serum levels were insignificantly different between HCV-positive and HCV-negative LP patients (p= 0.054). In conclusion, the significant elevation of serum AGA levels in LP patients reflects a possible link between LP and occult CD. Serum AGA (IgG) levels can be used as a marker of LP severity..

Reassessment of the cadmium toxicological reference value for use in human health assessments of foods

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 μg Cd/g creatinine for females aged 50–60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 μg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21–0.36 μg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63–1.8 μg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.

Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats

ObjectiveThe effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it disturbs homeostasis, thus resulting in inflammation and injury. MethodsMale rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA). ResultsOrally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8+ and CD4+ cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8+ and CD4+ cell number and TNF, IFN-γ and IL-17 cytokine production). ConclusionThese novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.

Novel insights into probabilistic health risk and source apportionment based on bioaccessible potentially toxic elements around an abandoned e-waste dismantling site

The study of potentially toxic element (PTE) hazards around e-waste recycling areas has attracted increasing attention but does not consider elemental bioaccessibility. Here, the respiratory and oral bioaccessibilities were incorporated into probabilistic health risk evaluation and source contribution apportionment. The results showed that soil Cd yielded the highest respiratory and oral bioaccessibility, whereas Cr in soils and vegetables attained the lowest oral bioaccessibility. When incorporating metal bioaccessibility into health risk assessment, a 48.3%–55.7% overestimation of non-cancer and cancer risks can be avoided relative to the risk assessment based on the total concentrations of PTEs. More importantly, priority control metals were misidentified without consideration of bioaccessibility. Cadmium, As, and Cr were screened as the priority metal(loid)s for targeted risk control based on the total PTEs, whereas Cd, Zn, and Cu were the priority metal(loid)s based on the bioaccessible PTEs. Furthermore, source apportionment revealed that >50% of oral bioaccessible Cd, Cu, Ni, Pb, and Zn in farmland were contributed by e-waste dismantling activities, whereas bioaccessible As and Cr mainly originated from agrochemical applications and natural sources, respectively. This study emphasizes the refinement of risk estimation and source apportionment through metal bioaccessibility adjustment, which facilitates the realistic assessment of adverse health effects in humans and the precise identification of high-risk sources.

A novel chronic in vivo oral cadmium exposure-washout mouse model for studying cadmium toxicity and complex diabetogenic effects

Type II diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction and hyperglycemia. In addition to well known risk factors such as lifestyle and genetic risk score, accumulation of environmental toxicants in organs relevant to glucose metabolism is increasingly recognized as additional risk factors for T2DM. Here, we describe the development of an in vivo oral cadmium (Cd) exposure model. It was shown that oral Cd exposure in drinking water followed by washout and high fat diet (HFD) in C57BL/6N mice results in islet Cd bioaccumulation comparable to that found in native human islets while mitigating the anorexic effects of Cd to achieve the same weight gain required to induce insulin resistance as in Cd naïve control mice. Inter individual variation in plasma glucose and insulin levels as well as islet Cd bioaccumulation was observed in both female and male mice. Regression analysis showed an inverse correlation between islet Cd level and plasma insulin following a glucose challenge in males but not in females. This finding highlights the need to account for inter individual target tissue Cd concentrations when interpreting results from in vivo Cd exposure models. No effect of Cd on insulin secretion was observed in islets ex vivo, highlighting differences between in vivo and ex vivo cadmium exposure models. In summary, our oral in vivo Cd exposure-washout with HFD model resulted in islet Cd bioaccumulation that is relevant in the context of environmental cadmium exposure in humans. Here, we showed that islet Cd bioaccumulation is associated with complex cadmium-mediated changes in glucose clearance and β-cell function. The model described here will serve as a useful tool to further examine the relationship between Cd exposure, islet Cd bioaccumulation, dysglycemia and their underlying mechanisms.

Nigella sativa oil protects against cadmium-induced intestinal toxicity via promotion of anti-inflammatory mechanisms, mucin expression and microbiota integrity.

Objective:This study examined the protective effects of Nigella sativa oil (NSO) on cadmium (Cd)-induced alterations affecting gut morphology and microbiota composition, as well as the involvement of mucus glycoprotein (MUC2) and immuno-inflammatory markers (TNFα and IL-2) in the colon of rats.Materials and Methods:Male Wistar rats, randomized into four groups, were treated either with distilled water (control), CdCl2 (100 mg/kg), CdCl2+NSO (1 ml/kg) or NSO alone. After the experiments, faecal samples were processed for microbial culture on various selective media, while intestinal segments were prepared for histopathological examination and immunohistochemistry. The composition of NSO was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS).Results:Oral Cd administration provoked dramatic increases in faecal counts of potentially pathogenic bacteria (Staphylococci, Enterococci, Pseudomonas and Escherichia coli), while decreasing probiotic lactobacilli counts. Cadmium treatment caused down-regulation of colonic MUC2 (p=0.003) and IL-2 (p=0.03), but increased TNFα (p=0.034), along with reduced goblet cell counts and mucus production. Conversely, treatment with NSO significantly improved Lactobacilli counts (p=0.042), while reducing the levels of potentially pathogenic species. In addition, NSO significantly restored colonic expressions of MUC2 (p=0.001), TNFα (p=0.007) and IL-2 (p=0.025) to control levels. GC-MS analysis of NSO revealed the presence of the active ingredient, thymoquinone and a high content of unsaturated fatty acids, including trans-13-octadecenoic acid and oleic acid. Conclusion:This study highlights the intestinal mucus, microbiota and immuno-inflammatory system as important protective targets of NSO against Cd-induced intestinal toxicity.

Condensed Tannins Improved Immune Functions and Reduced Environmental Pollution of Captive Sichuan Black Goat Kids Under Cadmium Toxicity

To investigate the effects of condensed tannins (CT) on immune functions and nitrogen (N) emissions of captive Sichuan black goat kids under cadmium (Cd) toxicity, a total of 18 Sichuan black goat kids (2months old, 9.6 ± 1.2kg) were randomly used in this 30-day trial. The dietary treatments were (1) CON group, basic diet; (2) Cd group, basic diet + oral 10mg Cd/kg·BW; and (3) CT group, Cd group + 400mg/kg CT. Oral Cd supplementation significantly decreased the Cu and Fe contents in serums and livers of captive Sichuan black goat kids (P < 0.05), but adding CT in the Cd group increased the Fe and Mo contents and decreased the Cd content in serums and livers (P < 0.05). Additional CT supplementation in the Cd group extremely increased the activities of serum SOD, GSH-Px, and CAT (P < 0.05), and greatly decreased the serum MDA content (P < 0.05). The CT supplementation in the Cd group also extremely increased the concentrations of serum IgG, IgM, and IgA (P < 0.05), and greatly decreased the contents of IL-6, IL-1β, and TNF-α in serums (P < 0.05). Adding CT in the Cd group significantly increased the apparent digestibility of CP and EE and decreased the urinary nitrogen (UN) content (P < 0.05, Table 7). In conclusion, the application of additional CT improved antioxidant capacities and immune functions of captive black goats under Cd toxicity, then reduced the oxidative stress and toxic damage of Cd contamination. CT also improved the N digestibility and reduced the N emission, which was helpful to reduce environmental pollution.

Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats

ObjectiveThe aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. MethodsDetermination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. ResultsCd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. ConclusionThe potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.

Orofacial granulomatosis: a questionnaire study among\xa0Norwegian dental clinicians

AimsTo evaluate awareness on orofacial granulomatosis (OFG) and oral Crohn disease (oral CD) among Norwegian dental clinicians.MethodsA precoded questionnaire (QuestBack) was sent electronically to dentists and dental hygienists treating children and adolescents in the public dental service (PDS) in Norway. Data on the clinicians’ knowledge of OFG and oral CD related to working experience were analysed by Chi square tests and bivariate logistic regression analyses.ResultsA total of 1097 clinicians were invited to participate, 778 dentists and 319 dental hygienists; 48.2% returned the completed form. Fifty-four percent of the participants had ≥ 10 year experience of clinical practice. Two-thirds (68.4%) of the dentists and all but one of the dental hygienists graduated in Norway. Approximately half of the respondents were aware of OFG (41.2%) and oral CD (57.8%). One-quarter (24.6%) reported that they most likely had seen a patient with OFG and 20.6% with oral CD. Recently graduated dentists (≤ 10 years ago) were more aware of OFG and oral CD than those who graduated > 10 years ago (p ≤ 0.001). Regarding dental hygienists, this difference was observed for OFG only (p < 0.05). Country of education did not affect the clinicians’ reported knowledge. Approximately 90% would refer a patient suspected of having OFG or oral CD either to a dental specialist or to a physician.ConclusionThe high prevalence of clinicians observing OFG and oral CD in this study may indicate that OFG and/or oral CD are under-reported and that OFG in particular is more common than hitherto believed. The high frequency of awareness was promising for the benefit of the patients.

Subchronic Exposure to Cadmium Causes Persistent Changes in the Reproductive System in Female Wistar Rats.

Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5 mg/kg b.w. on the balance of sex hormones by estimating estradiol (E2) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17β-E2. Additionally, the uterine weight, histopathological changes in the uterus and ovaries, the regularity of the estrous cycle, Cd bioaccumulation in uterine tissue, and selected biochemical parameters of oxidative stress were determined. A long period of observation (three and six months following the administration period) was used to assess whether the existing effects are reversible. The lowest dose of Cd caused effects similar to 17β-E2: an increase of E2 concentration in the uterus, endometrial epithelium thickness, and disturbed estrous cycle with estrus phase prolongation. The obtained results suggest that Cd causes nonlinear response. Higher doses of Cd caused a significant decrease in E2 concentration in the uterus and plasma, estrous cycle disturbances, endometrium atrophy, and structural damage in the ovaries. This dose additionally induces lipid peroxidation in the uterine tissues. It is noteworthy that a prolonged time of observation after terminating the exposure showed persistent changes in the concentration of E2 in uterine tissue, as well as alterations in estrous cycle phases, and an increase in lipid peroxidation in the uterus. Moreover, significant positive correlations between the plasma E2 concentration and endometrial epithelium thickness in all studied groups were found. In summary, subchronic oral Cd exposure of female rats may result in impaired fertility processes.

Subacute Testicular Toxicity to Cadmium Exposure Intraperitoneally and Orally.

The toxic effects of cadmium (Cd) on reproductive parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.), although human intoxication occurs preferentially by the oral route and can be continuous. However, little is known about the effect of Cd administration routes on the testicular structure. Thus, this study investigated the testicular impact of Cd exposure comparing both i.p. and oral routes, both single dose (SD), in addition to the oral route in fractional doses (FD). Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral SD, and 4.28 mg/kg oral FD for 7 consecutive days. The Cd bioaccumulation was observed in all routes, mainly in the oral FD route. The concentrations of testicular Ca and Cu decreased in all animals exposed to Cd, while Zn and Mn decreased only in the i.p. route. Testicular SOD activity was reduced in both routes of oral administration, while CAT increased in the i.p. route, and GST increased in all animals exposed to Cd. Changes in the tubular parameters and cell viability were observed in both routes of Cd administration but were more intense in the oral route, mainly in the FD. Serum testosterone concentration was reduced in both routes of oral administration. Tubular damage, such as the vacuolization of the seminiferous epithelium, germ cell detachment, and seminiferous tubule degeneration, occurred in all groups exposed to Cd. Therefore, the oral Cd administration presented greater potential to promote testicular damage, mainly when the metal was given in a fractionated way.

Cadmium at Human Dietary Levels Disturbed Homeostasis of Nutritional Metals in Lung (P24-055-19)

ObjectivesMultiple metals are present in the human diet, with some being required as essential inorganic nutrients and all causing toxicity in excess or deficiency. Cadmium (Cd), a toxic heavy metal accumulates in human organs, kidney, liver and lung via food consumption. Our recent mouse studies showed that Cd decreased lung selenium level, and caused metabolic and transcriptomic disruption. However, little is known about the effects of Cd on nutritional metal distribution and subsequent impact on human health. In this study, we examined effects of oral Cd on distribution and interaction of nutritional metals in mouse lung. MethodsC57BL/6 J mice were treated with Cd at low concentrations (0, 1, 3.3, 10 mg CdCl2/L) by drinking water for 16 weeks. Lungs were collected from mice and lung samples and isolated lung mitochondria were analyzed for 25 inorganic nutritional and toxic environmental metals by inductively coupled plasma mass spectrometry (ICP-MS). In addition, human lung samples from the Emory Transplant Program (Emory IRB 0,0006248) and from International Institute for Advancement of Medicine were analyzed for metals by ICP-MS. ResultsLungs (n = 50) from mice exposed to Cd in a dose-response study showed that cobalt (Co), vanadium (V), copper (Cu) and molybdenum (Mo) were positively correlated with Cd [Spearman correlation (r); 0.38, 0.31, 0.42, 0.41, P < 0.05], and correlation of V and Cu to Cd were increased in lung mitochondria (r; 0.73, 0.87). The data for human lungs (n = 24) showed that Cd was positively correlated with Co, V and manganese (Mn), r; 0.43, 0.73 and 0.39, P < 0.05) in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, emphysema, cystic fibrosis, and negatively correlated with magnesium (r = −0.46). ConclusionsThe results show that Co and V each had positive correlations with Cd in human and mouse lung studies, and interactions of metals with Cd were increased in lung mitochondria. Additionally, the results suggest interactions of Cd with Cu, Mo and Mn, which could impact the function of these essential nutrients. Given the range of toxic effects of Cd, the results indicate that studies are needed to understand potential dysfunctions related to disturbed homeostasis of nutritionally essential metals. Funding SourcesNIEHS R01 ES023485 and NIEHS R21 ES025632.

Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy.

Purpose:To evaluate the efficacy and safety of orally administered grape seed proanthocyanidin extract (GSPE) in patients with non-proliferative diabetic retinopathy (NPDR).Methods:In this randomized (1:2:2), multicentre, double-blind trial, patients (n = 124; age: 40–78 years) were administered placebo, calcium dobesilate (CD; 750 mg/d), or GSPE (150 mg/d) orally for up to 12 months. All patients had retinal thickening with hard exudates (HEs) that met predefined criteria; the median best-corrected visual acuity was 0.8, as assessed using the Snellen visual acuity card. The main outcome measure was an improvement in HEs by at least 1 grade on a 10-grade severity scale. This was evaluated using fundus photography over 1 year.Results:The rate of improvement in the HE severity was higher in the GSPE group than in the CD group. No statistically significant difference existed among the study groups in optical coherence tomography parameters, such as central subfield macular thickness and total macular volume (TMV). However, in the GSPE group, TMV after 9 months of treatment was significantly decreased compared with that at baseline. The GSPE group showed a significantly greater improvement in HE severity than did the placebo or CD group. Four cases in the GSPE group and 2 in the CD group were determined to have developed potential treatment-related adverse reactions, which were all gastrointestinal in nature.Conclusions:Oral GSPE therapy for 1 year improved HEs in patients with NPDR. The efficacy of GSPE for HEs was higher than that of oral CD in the study patients.

Cadmium-Induced Testicular Toxicity in Mice: Subacute and Subchronic Route-Dependent Effects

This study aimed to compare Cd exposure by intraperitoneal (i.p.) and oral routes, evaluating the testicular subacute and subchronic effects. Adult male mice were separated into three groups subdivided according to the experimental period (7 and 42days after Cd exposure: subacute and subchronic effects, respectively): one group received water and two groups received CdCl2 (1.2mg/kg i.p. and 24mg/kg oral). The testicular concentration of essential minerals and Cd, activity of antioxidant enzymes and markers of oxidative stress, histology, and testicular histomorphometry were evaluated. The subacute effect of oral Cd showed reduced Fe concentration, while Ca and Cu increased in this route. The subchronic effect promoted decreasing in Mg in i.p. and oral routes, whereas Zn decreased only in the oral, and the Fe concentration did not change. SOD activity decreased in the oral subacute evaluation and in both pathways, i.p. and oral routes, in the subchronic evaluation, while GST activity increased, and MDA concentration decreased. Labeling of apoptotic cells was increased in the subacute and subchronic evaluation. Seminiferous epithelium degeneration, death of germ cells, and Leydig cell damages occurred in i.p. and oral routes. However, these damages were more intense in the oral route, mainly evaluating the subchronic effects. The results confirm that the severity of Cd-induced testicular injury depends on the pathway, as well as the duration of exposure.

The effect of repeated cadmium oral exposure on the level of sex hormones, estrous cyclicity, and endometrium morphometry in female rats

Cadmium (Cd) is regarded as a potential endocrine disruptor. However, the exact mechanism by which this metal may interfere with the reproductive system has not yet been elucidated. The present study aimed to investigate the effect of subacute Cd oral administration at daily doses of 0.09, 1.8, and 4.5 mgCd/kg b.w. and the impact of Cd on sex hormones (estradiol (E2) and progesterone (P)) in the plasma and uterus, as well as on estrous cyclicity and histopathological changes in uterine and ovary in female rats after terminating the exposure and after a prolonged observation period (3 months). Moreover, Cd bioaccumulation in the uterine and brain tissue of rats was analyzed. The study revealed that oral Cd exposure induced changes in the plasma levels of steroid hormones: decrease in E2 and increase in P after the highest dose of Cd. Probably, for the first time, it was evidenced that circulation sex hormone disturbances in Cd-exposed rats caused irregular estrous cycle, persisting for 3 months after exposure termination; no alterations in these hormone levels in uterine tissue were noted. Cd did not induce estradiol-like hyperplasia of endometrium, but resulted in endometrial edema irrespective of the dose, and caused damage of the ovaries after the highest dose. In summary, subacute oral exposure of female rats to Cd may lead to long-term disturbances in reproductive system.

Successful treatment of oral Crohn's disease by anti-TNF-alpha dose escalation - a case report

BackgroundCrohn’s Disease (CD) is typically characterized by abdominal symptoms, however, besides gastrointestinal symptoms, CD patients may suffer from extraintestinal manifestations which are far less common and medical treatment can be challenging.Case presentationWe report about a 34-year-old Crohn’s Disease (CD) patient in clinical remission under adalimumab therapy who presented in the clinic for Cranio-Maxillo Surgery due to severe pain in the mandibular area. Ulcerative lesions of the buccal-side mucosa of the right mandible were detected. To rule out malignancy, a biopsy was obtained and revealed ulcerative stomatitis with noncaseating granulomas consistent with oral CD. Shortening the adalimumab administration interval to weekly injections resulted in a complete healing of the oral CD lesions without residual inflammation.ConclusionThe case presented here demonstrates that gastroenterologists should evaluate and consider oral CD lesions as a possible marker of disease activity in patients despite having quiescent intestinal CD.

The Effect of Cadmium on the Ultrastructure and Metallothionein Levels in the Liver and Kidneys of Japanese quail

Background: The aim of this study was to use Japanese quail as an animal model to evaluate the effects of cadmium (Cd) on the ultrastructure and the activity of metallothionein (MT) in the liver and kidneys. Methods: One hundred male Japanese quails were randomly divided into two Cd and control groups in 2015. The first group received 100 ppm Cd for 60 days in their feed. The ultrastructural changes of the liver and kidneys of Japanese quails were examined by the transmission electron microscope and the concentration of MT in these organs was measured. Results: The ultrastructural alternations of the liver included distension of rough endoplasmic reticulum (RER), mitochondrial swelling and lack of cristae, nuclear chromatin compression, and margination, the increased fat vacuole and damage to intercellular bindings. The kidneys ultrastructural alterations were mitochondrial swelling and damage to the cristae, the increased number of lysosomes, nuclear chromatin compression and margination, the decreased number of microvilli, and cell death. The concentration of MT and Cd in the liver and kidneys of the Cd group was significantly higher than that of the control group (P<0.05). A positive correlation was observed between the increased concentration of Cd and MT in the liver and kidney tissues. Conclusion: The use of oral Cd caused an alternation in the ultrastructure and increased the concentration of Cd and MT in the liver and kidneys of Japanese quail.

The Ameliorative Effect of Cleome Droserifolia (Samwa) on Myocardial Injury Associated with Diabetes in Male Rats

Background: Diabetes is an imperative risk factor for cardiac complications development. Cleome droserifolia (Cd) is used in Egyptian traditional medicine for treatment of diabetes mellitus. Aim: The aim of the present study was to measure the possible protective effects of ethanolic extract of Cd against cardiacmyopathy in Streptozotocin (STZ) induced diabetic rats. Materials and Methods: Experimental diabetes was induced by intrapritoneal injection with a single dose of STZ (45 mg/kgbw). Oral dose Cd extract was administered daily for four weeks (310 mg/kg bw). Results: Diabetic rats exhibited an increase in glucose level and lipid profile as well as cardiacpro-inflammatory, pro-apoptotic markers and oxidative stress, while a decrease was recorded in antioxidant enzymatic activities. On the other hand the administration of diabetic rats with Cdextract for four weeks resulted in a significant amelioration in the most of the parameters mentioned above when compared with diabetic rats. Conclusion: The data clearly indicated that the treatment with Cleome droserifolia exerts a therapeutic protective nature in cardiac complications due to diabetes by decreasing oxidative stress and cardiac damage which may be attributed to its antioxidative potential.