Safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke

Stroke is the third cause of death and the leading cause of disability in adult subjects. Although stroke mortality has been declining in some countries, stroke morbidity has been increasing due to the aging of population and patients improved survival. Treatment with recombinant tissue plasminogen activator (rtPA) is successful provided it is administered within 3 hours of symptoms onset, but its use is limited to about 5% of the patients with acute ischemic stroke. Furthermore, no neuroprotective agent has yet been proven effective in human clinical trials. The development of other therapeutic strategies is, therefore, warranted. The use of stem cells in animal models has led to functional improvement following stroke. Recent publications have shown that bone marrow mononuclear cells (BM-MNC) therapy through intracoronary injection is a safe procedure in patients with acute or chronic ischemic heart disease. Based on these preliminary data, there has been growing interest in the study of BM-MNC transplantation for acute ischemic stroke. We report the first case of intra-arterial autologous BM-MNC transplantation for acute ischemic stroke.     

Renal involvement in primary Sjogren syndrome of childhood: case report and literature review

Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and nephrogenic diabetes insipidus secondary to SS-associated tubulointerstitial nephritis. Immunosupressive treatment and alkali/electrolyte supplementation resulted in stable renal function over the 6-year follow-up. A review of the literature focuses on two aspects of pSS: (1) the difficulties in diagnosing pSS in childhood and (2) clinical–pathological features, treatment and outcome of renal tubulointerstitial disease in childhood pSS. SS should be considered in older children, particularly females with otherwise unexplained RTA. A careful search for other renal dysfunctions is necessary, and renal biopsy may be of value in assessing the extent of renal damage and the need for immunomodulatory therapy.     

Autologous stem cell‐based therapy for sickle cell leg ulcer: a pilot study

Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6‐month follow‐up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45^low and fibroblast colony‐forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.     

Ultrastructure of regenerated bone mineral surrounding hydroxyapatite-alginate composite and sintered hydroxyapatite

We report the ultrastructure of regenerated bone surrounding two types of biomaterials: hydroxyapatite-alginate composite and sintered hydroxyapatite. Critical defects in the calvaria of Wistar rats were filled with micrometer-sized spherical biomaterials and analyzed after 90 and 120 days of implantation by high-resolution transmission electron microscopy and Fourier transform infrared attenuated total reflectance microscopy, respectively. Infrared spectroscopy showed that hydroxyapatite of both biomaterials became more disordered after implantation in the rat calvaria, indicating that the biological environment induced modifications in biomaterials structure. We observed that the regenerated bone surrounding both biomaterials had a lamellar structure with type I collagen fibers alternating in adjacent lamella with angles of approximately 90°. In each lamella, plate-like apatite crystals were aligned in the c-axis direction, although a rotation around the c-axis could be present. Bone plate-like crystal dimensions were similar in regenerated bone around biomaterials and pre-existing bone in the rat calvaria. No epitaxial growth was observed around any of the biomaterials. A distinct mineralized layer was observed between new bone and hydroxyapatite-alginate biomaterial. This region presented a particular ultrastructure with crystallites smaller than those of the bulk of the biomaterial, and was possibly formed during the synthesis of alginate-containing composite or in the biological environment after implantation. Round nanoparticles were observed in regions of newly formed bone. The findings of this work contribute to a better understanding of the role of hydroxyapatite based biomaterials in bone regeneration processes at the nanoscale.     

Re-use of the original infusional induction chemotherapy as salvage therapy in myeloma patients relapsing after one autograft

If standard infusional therapy (IC) has been used to treat myeloma at presentation, it is a matter of debate whether patients should receive the original induction therapy or a different drug combination in first relapse. Instinctively, most clinicians may switch treatment, particularly since the advent of new drugs for the treatment of myeloma. Hitherto, there has been no data on the efficacy of repeating standard IC in the salvage setting.

We studied 62 myeloma patients whose initial treatment consisted of C-VAMP and a single high dose melphalan procedure and who were retreated with C-VAMP at the time of first relapse. Response to salvage C-VAMP was seen in 50% (95% confidence interval = 0.37–0.62) but we were unable to identify any predictors for response to salvage C-VAMP. Only patients resistant to salvage C-VAMP benefited from a second autograft. The survival of patients who responded to salvage C-VAMP was not prolonged by a second transplant.

In conclusion, our data supports the use of C-VAMP for patients with myeloma in first relapse and suggest that only patients resistant to salvage C-VAMP should be offered a second autograft.     

Malignant Tumors in Families of Thyroid Cancer Patients

A case-control study comprised 177 patients with various types of thyroid cancer and the same number of hospital controls individually matched by age, sex and place of residence. Malignant tumors were more frequent among first and second degree relatives of cases as compared to controls. The odds ratio (95% confidence interval) was 2.43 (1.33-4.44) and 5.33 (1.77-16.01) respectively. The most frequent were cancers of uterus and stomach with odds ratio of 6.00 (1.61-22.36) and 9.00 (1.64-49.35). Thyroid cancer was present only in first-degree relatives of two cases and none of controls.     

Conjugation of tomatine with l(+)-lactic acid by Nocardia restricta

Nocardia restricta conjugates tomatines with l(+)-lactic acid, which represents a new mode of bioconversion of steroid glycosides. The specifity in cell-free homogenate was not restricted to α-tomatine, since δ-tomatine was transformed to the conjugated metabolite as well. It was shown with inhibitors of protein synthesis that the enzymes responsible for this reaction are constitutive. By using protoplasts and centrifugation it was found that the conjugating activity and the reaction products were bound to the membrane part of the 10,000 × g sediment of the cell-free homogenate. Possible mechanisms as well as the biological significance of this reaction are discussed.     

Ochratoxin A in human blood and Balkan endemic nephropathy

The etiology of Balkan endemic nephropathy, a kidney disease encountered among the rural population living in regions along several big rivers on the Balkan Peninsula, remains unknown in spite of many hypotheses put forward and tested. One hypothesis involves mycotoxins as the causal agent. The mycotoxin ochratoxin A has been demonstrated to have a potent nephrotoxic effect in all mammalian species tested so far.The results of analysis of ochratoxin A in human blood samples by an analytical method based on the measurement of fluorescence spectra, before and after incubation with carboxypeptidase A, is described. For a 2-g-sample the detection limit of the method is 1–2 ng/g serum. High performance liquid chromatography used for the confirmation of ochratoxin A identity by means of several derivatives of the molecule is also described. Out of more than 600 samples collected in an endemic region in Yugoslavia about 7% were positive for ochratoxin A. The highest concentration found was 40 ng ochratoxin A/g serum.     

Photosynthetic parameters as indicators of trinitrotoluene (TNT) inhibitory effect: Change in chlorophyll a fluorescence induction upon exposure of Lactuca sativa to TNT

Trinitrotoluene, as a compound of conventional explosive, may cause inhibitory effect on terrestrial plants. When Lactuca sativa was exposed to different concentrations of trinitrotoluene (32–1000 mg/kg), photosynthetic process was investigated by using rapid chlorophyll fluorescence kinetic and pulse modulated fluorometry. The decrease of chlorophyll a variable fluorescence was seen to be caused by the deactivation of photosystem II reaction centers. We found for rapid variable fluorescence to be a useful indicator to evaluate the inhibitory effect of trinitrotoluene on photosystem II primary photochemistry and electron transport. The fluorescence parameters, related to the reduction state of photosystem II and to non-photochemical dissipation of light energy, showed a strong relation between the inhibitory effect of photosystem II activity and concentration of trinitrotoluene. The change of photosynthetic fluorescence parameters induced by trinitrotoluene was a reliable indication of the plant physiological state. We proposed for the reduction state of photosystem II and the non-photochemical energy dissipation to be a useful tool in bioassay toxicity testing of trinitrotoluene polluted soil.