Influence of lead on calcium and strontium transfer through the duodenal wall in rats

Five-week-old female albino rats were given daily doses for 1 or 2 weeks of lead as acetate ranging from 2 μg to 40 mg by gastric intubation and sacrificed on the 8th or 15th day of the experiment. Calcium-45 and ⁸⁵Sr were used as markers to assess the calcium and strontium transfer through the duodenal wall by the everted gut sac method of Wilson and Wiseman. Doses of lead acetate greater than 20 μg per day decreased the transfer of both calcium and strontium across the duodenal wall and these transfers decreased further with increased doses of lead, an effect which was independent of whether the rats were killed on the 8th or 15th day of the experiment. Doses of lead acetate greater than 200 μg per day, however, did not produce a further decrease in these transfers. The retention of both calcium and strontium in the intestinal wall was unaffected by the lead treatment.     

Intestinal Perforation Secondary to Blunt Inguinal Trauma in a Soccer Player: A Case Report

Background: Intestinal perforation caused by blunt trauma to an inguinal hernia is a very uncommon event. Case Report: We present the case of a 55-year old man who suffered trauma to the inguinal area while playing soccer and later developed intense abdominal pain with no categorical signs of peritoneal irritation. Computed tomography scan at arrival showed a right inguinal hernia, with partial protrusion of the ileum, inflammatory changes of the mesenteric fat tissue inside the hernial sac, and free intraperitoneal fluid. Several hours later he developed hypotension and fever. An emergency laparotomy was performed, revealing ileum perforation with peritonitis. Intestinal perforation was repaired without intestinal resection. After surgery, the patient developed severe septic shock with multiple organ failure. He recovered without sequelae and was discharged 3 weeks later. Conclusion: This case emphasizes the potential clinical complications associated with this condition.     

Biological evaluation of transdichloridoplatinum(II) complexes with 3- and 4-acetylpyridine in comparison to cisplatin

Background

In our previous study we reported the synthesis and cytotoxicity of two trans-platinum(II) complexes: trans-[PtCl₂(3-acetylpyridine)₂] (1) and trans-[PtCl₂(4-acetylpyridine)₂] (2), revealing significant cytotoxic potential of 2. In order to evaluate the mechanism underlying biological activity of both trans-Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC-5 and MS1 cells.

Materials and methods.

The cytotoxic activity of the investigated complexes was determined using SRB assay. The colagenolytic activity was determined using gelatin zymography, while the effect of platinum complexes on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by quantitative real-time PCR. Apoptotic potential and cell cycle alterations were determined by FACS analyses. Western blot analysis was used to evaluate the effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR was used for the ERCC1 mRNA expression analysis. In vitro antiangiogenic potential was determined by tube formation assay. Platinum content in intracellular DNA and proteins was determined by inductively coupled plasma-optical emission spectrometry.

Results

Compound 2 displayed an apparent cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2 exerted antiproliferative effect through apoptosis induction, while 1 induced both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real-time PCR and Western blot, was associated with down-regulation of ERCC1. Both trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly abrogated in vitro tubulogenesis in MS1 cells.

Conclusions

The ability of 2 to induce multiple and selective in vitro cytotoxic effects encourages further investigations of trans-platinum(II) complexes with substituted pyridines.     

Enzyme replacement therapy in two patients with an advanced severe (Hurler) phenotype of mucopolysaccharidosis I

Although offered, two of our Hurler patients (OMIM 607014) had not undergone bone marrow transplantation at an early stage of their disease. Rapid disease progression had resulted in a range of signs and symptoms representative of advanced neurodegeneration and debilitating somatic Hurler disease. As general palliative care had only little impact on the burden of disease, laronidase (Aldurazyme) treatment was introduced in an attempt to alleviate somatic symptoms and to improve the quality of their lives. Therapeutic benefits from enzyme replacement therapy included improvements in general physical condition and mood, as well as normalisation of the sleep patterns, disappearance of sleep apnoea syndrome and reduction of hepatosplenomegaly. Improvements in the joint mobility were mainly limited to the wrists and hips. In addition, improvements in cardiac function, stool habits, visual acuity, corneal clouding and hearing were observed in one or both patients. Irreversible skeletal changes did not deteriorate. The neurological outcome of these patients is likely not influenced as laronidase is believed not to pass the blood-brain barrier. Therefore, the decision to initiate this therapy in transplant-naïve Hurler patients with an advanced stage of the disease should be taken after careful consideration. Conclusion: We are of the opinion that the option of enzyme therapy should not be excluded in severely affected Hurler patients who cannot undergo bone marrow transplantation. Stabilization or amelioration of somatic disease and improvement of the quality of their lives should be embraced as therapeutic goals.     

Regeneration of spleen colony-forming cells and granulocyte-monocyte progenitors in T-cell deprived mice treated with cyclophosphamide

The role of T cells in regeneration of CFU-S(d8) and GM-CFU was investigated in adult Cy treated mice. CBA mice were deprived of T cells by adult thymectomy and irradiation (TIR) and treated with 200 mg/kg Cy. The type of CFU-S(d8) and GM-CFU regeneration curve after Cy was not different from that found in nonthymectomized, irradiated (NIR) mice. The activity of a stimulator of CFU-S(d8) proliferation was increased to the same degree in the bone marrow of both TIR and NIR mice. However CFU-S(d8) recovered to a higher level in TIR than in NIR mice. The results presented demonstrate that T-cell depletion in adult mice influences CFU-S(d8) growth.