rac-1-[(2-Methoxyethyl)sulfanyl]-2-[(2-methoxyethyl)sulfinyl]benzene and its PdCl2 complex.

As an extension of recent findings on the recovery of palladium with dithioether extractants, single crystals of the chelating vicinal thioether sulfoxide ligand rac-1-[(2-methoxyethyl)sulfanyl]-2-[(2-methoxyethyl)sulfinyl]benzene, C(12)H(18)O(3)S(2), (I), and its square-planar dichloridopalladium complex, rac-dichlorido{1-[(2-methoxyethyl)sulfanyl]-2-[(2-methoxyethyl)sulfinyl]benzene-κ(2)S,S'}palladium(II), [PdCl(2)(C(12)H(18)O(3)S(2))], (II), have been synthesized and their structures analysed. The molecular structure of (II) is the first ever characterized involving a dihalogenide-Pd(II) complex in which the palladium is bonded to both a thioether and a sulfoxide functional group. The structural and stereochemical characteristics of the ligand are compared with those of the analogous dithioether compound [Traeger et al. (2012). Eur. J. Inorg. Chem. pp. 2341-2352]. The sulfinyl O atom suppresses the electron-pushing and mesomeric effect of the S-C-C-S unit in ligand (I), resulting in bond lengths significantly different than in the dithioether reference compound. In contrast, in complex (II), those bond lengths are nearly the same as in the analogous dithioether complex. As observed previously, there is an interaction between the central Pd(II) atom and the O atom that is situated above the plane.

Instability of beta E-messenger RNA during erythroid cell maturation in hemoglobin E homozygotes.

Hemoglobin E interacts with beta-thalassemia to produce a disorder of variable severity that is the most common form of symptomatic thalassemia in Southeast Asia. The beta E-globin gene acts as a mild thalassemia gene; there are low levels of beta E-messenger RNA (mRNA) in reticulocytes, and preliminary evidence had suggested that this might be due to instability of the beta E-mRNA. Analysis of beta E-mRNA levels in the nuclei and cytoplasm of bone marrow erythroblasts compared with reticulocytes has shown higher levels of beta E-mRNA in the former, providing direct evidence that this is the case.

Islet cell autoimmunity in type I diabetic patients after HLA-mismatched pancreas transplantation.

The aim of this study was to investigate a possible reenhancement of islet cell autoimmunity in type I (insulin-dependent) diabetic patients who received HLA-mismatched pancreas transplants from cadaveric donors and who underwent generalized immunosuppression. Circulating islet cell antibodies (ICA) and complement-fixing ICAs (CF-ICAs) have been tested at 1, 2, 3, 6, and 12 mo and at least once a year posttransplantation in 23 recipients of 25 transplants (22 simultaneous with kidney, 2 retransplants, 1 isolated; 23 segmental neoprene injected, 2 whole with enteric drainage). Patients were aged 35.3 +/- 1.9 yr with a duration of diabetes of 20.6 +/- 1.1 yr. Immunosuppression consisted of double or triple association of azathioprine, cyclosporin, and prednisone with or without temporary antilymphocyte globulins. The number of HLA-A and HLA-B compatibilities was none in 8 patients, one in 12 patients, two in 4 patients, and three in 1 patient. The mean follow-up was 4.0 +/- 0.4 yr/patient (range 0.4-7.2). ICAs were positive pretransplantation in 2 of 25 patients and reappeared 1-42 mo posttransplantation in another 7. In 6 patients, CF-ICAs were also positive. In 7 of 9 ICA+ patients the pancreas transplant failed; in 1 patient this occurred 4 mo before ICA reappearance, and in 6 patients it occurred 2-35 mo after the first detection of ICAs. Pancreas-transplant failure was significantly associated with the positivity for ICAs (P less than .05) and particularly for CF-ICAs (P less than .005). ICA positivity was transitory in 4 patients (2-27 mo) and persistent in the remaining 5 (up to 61 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

High bone turnover associated with an aluminum-induced impairment of bone mineralization.

A hemodialyzed patient showing x-ray and biochemical evidence of apparently pure severe hyperparathyroidism underwent a tetracycline-labeled transiliac bone biopsy. The bone biopsy not only confirmed the hyperparathyroid bone lesions but also revealed an impairment of bone mineralization induced by aluminum. This was demonstrated by a reduction of double-labeled osteoid surfaces, a significant increase in the osteoid seam thickness, and the presence of extensive aluminum deposits in bone. The planned parathyroidectomy was postponed, and deferoxamine (DFO) therapy, 2 g once a week, was initiated. A second bone biopsy, taken 6 months later, showed recovery of normal bone mineralization but the persistence of hyperparathyroid bone lesions. This was associated with a considerable reduction in the extent of aluminum deposits on trabecular bone surfaces. This observation shows that severe and apparently pure hyperparathyroidism can be associated with an impairment of bone mineralization induced by aluminum. This suggests that bone mineralization and aluminum overload should be evaluated in dialyzed patients who are being considered for parathyroidectomy.

Thrombocytopenia, macrothrombocytopathia, nephritis and deafness.

The association of thrombocytopenia, macrothrombocytopathia, nephritis and deafness is rare. Reported here is a new case of this triple association. The clinical course, the nephropathologic findings and the bilateral neurologic hearing loss were similar to those already reported, with a slowly progressive impairment of renal function accompanied by a persistent proteinuria. The platelet diameters were increased. These macroplatelets contained granules of normal structure but with an irregular distribution in the cytoplasm. In other areas the cytoplasm was rich in surface connected system. The survival of these platelets and their contraction were normal. Their aggregation and excretion in response to collagen, adenosine diphosphate and thrombin, and the values of platelet factor 3 activity were all decreased. The degranulation defect, also present, was observed in the absence of a decrease in intracellular cyclic adenosine 5'-monophosphate (AMP) suggesting a relationship between these two findings.

Cyclosporine plasma levels six hours after oral administration. A useful tool for monitoring therapy.

Clinical evolution and cyclosporine (CsA) monitoring of 65 transplanted patients (55 kidneys, and 10 kidneys and pancreases) treated with CsA were analyzed retrospectively (45 patients) and prospectively (34 patients). Our results showed the following: (1) nephrotoxicity is not uncommon even with low trough plasma levels of CsA; (2) the T6 value of a CsA pharmacokinetic plasma curve (6 hr after oral drug administration) is a valid expression of a full pharmacokinetic study; (3) when T6 was used prospectively as a monitoring tool and dose adjustments made disregarding concomitant serum creatinine levels, the latter decreased when CsA dose adjustments were made to correct toxic (greater than 350 ng/ml) or subtherapeutic (less than 100 ng/ml) T6, P less than 0.01. At present, serum creatinine for all our patients is 180.2 +/- 8 mumol/L, and no patient has needed to be switched to conventional treatment. The validity of trough plasma levels in patients under CsA oral administration once or twice a day seems questionable, and T6 proved to be more useful. Thus nephrotoxicity and CsA undertreatment may be avoided. This new monitoring tool (T6) will allow the utilization of lower doses of CsA and thus contribute to improved long-term graft function.

Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients--a two-year follow-up.

We have investigated the metabolic effects of segmental (neoprene-injected) pancreas transplantation versus whole (enteric-diverted) pancreas transplantation. Seventeen uremic insulin-dependent diabetes mellitus (IDDM) patients received a simultaneous pancreaticorenal transplant: in a prospective, randomized study, 9 patients received a segmental neoprene-injected graft (group A) while 8 patients received a total pancreaticoduodenal graft, with enteric diversion (group B). The immunosuppressive therapy was based on ALG, CsA, azathioprine, and steroids. Three months after surgery, patients were submitted to the following metabolic investigation: i.v. and oral glucose tolerance tests, Hba1, i.v. arginine test, and a 24-hr metabolic profile. The OGTT, HbA1, and metabolic profile were repeated 12 and 24 months after transplantation. At 3 months after transplantation, the OGTT showed delayed insulin secretion and higher blood glucose levels in group A. Serum insulin levels after IVGTT or arginine were higher in group B than in group A. OGTT at 12 and 24 months were unchanged in group B, while in group A a higher incidence of impaired glucose tolerance (IGT) and diabetes mellitus response were observed. HbA1 and blood glucose levels during the 24-hr profile showed good metabolic control in both groups at 3, 12, and 24 months. We can conclude that both the segmental and total pancreas transplantation restore a good metabolic control in IDDM patients, though a higher incidence of IGT and DM responses were observed after OGTT in the patients receiving a segmental graft. These abnormalities do not seem to interfere with metabolic control in everyday life. These results seem to be the consequence of the different B cell masses transplanted with these two techniques.

A method for early detection of graft failure in pancreas transplantation.

Pancreatic transplantation is intended to normalize carbohydrate metabolism in insulin-dependent diabetics by restoring endogenous insulin release, and it is usually performed together with kidney transplantation in patients with end-stage renal failure. A major problem in these patients is the daily control of the grafted pancreas because traditional measurements do not appear to be adequate to evaluate pancreatic function. Aiming at early detection of graft failure, we have analyzed in 8 such patients and in 20 nondiabetic kidney-grafted patients (a control group) the following variables: 24-hr glycosuria (absolute values, or values after natural logarithmic transformation) and 24-hr urinary C-peptide excretion (corrected for 24-hr urinary creatinine). These measurements, considered alone, did not detect pancreatic graft failure; for instance, glycosuria can depend on immunosuppressive steroid treatment, and it was often found even in the control group. On the contrary, the ratio Ln 24-hr glycosuria: 24-hr urinary C-peptide varied from 0.00 to 0.18 in the control group and in normally working pancreatic grafts; when the pancreatic grafts failed, however, as confirmed by arteriographic evidence, histologic findings, or dynamic endocrine tests, this ratio rose far higher than 0.18, reaching values as high as 12.2. Use of this ratio provides a simple technique for daily evaluation of pancreatic graft function and for early detection of graft failure.

Short daily hemodialysis and nutritional status.

Daily hemodialysis improves clinical outcomes in dialysis patients. This study shows the results of 10 patients who underwent short daily hemodialysis (SDHD) from 23.2 +/- 13 months and focuses on nutritional status under this strategy. With SDHD, patients had an increase in energy and protein intake confirmed by an increase in dry weight and lean body mass. Additional clinical improvement was obtained for blood pressure control, regression of left ventricular hypertrophy, correction of anemia, and better quality of life. These biological and clinical improvements are mainly the results of a higher frequency of dialysis sessions. The nutritional improvements with disappearance of anorexia are the consequence of general well being, less dietetic constraints, and less drugs prescribed. Short daily hemodialysis offers an adequate and more physiological strategy and may be considered for improving nutritional status in selected patients.

Formation of the 3-Pentanone ion from ionized propyl propanoate through Ion-Neutral complexes.

Formation of the 3-pentanone ion (3) from ionized propyl propanoate through the complex [C2H5CO(+) (•)OC3H7] is proposed based on data obtained by photoionization. The threshold and energy dependence for forming 3 relative to those for related processes support this proposal. The threshold for forming 3 coincides with that predicted for forming [CH3CH2CO(+) (•)CH2CH3], suggesting that that complex is also an intermediate in the pathway to 3. 3-Pentanone ion formation is important much further above threshold than is alkane elimination through [RCO(+) (•)R] complexes. This adds to evidence that reactions between the partners in ion-dipole complexes take place over a wider energy range than do such reactions in complexes containing nonpolar neutral partners.

Isomeric ion-neutral complexes generated from ionized 2-Methylpropanol and n-Butanol: the effect of the polarity of the neutral partner on complex-mediated reactions.

Photoionization was used to characterize the energy dependence of C3H 7 (+) , C3H 6 (+) , CH3OH 2 (+) and CH2=OH(+) formation from (CH3)2)CHCH2OH(+•) (1) and CH3CH2CH2CH2OH(+•) (2). Decomposition patterns of labeled ions demonstrate that close to threshold these products are primarily formed through [CH 3 (+) CHCH3 (•)CH2OH] (bd3) from 1 and through [CH3CH2CH2 (•)CH2=OH(+)] (9) from 2. The onset energies for forming the above products from 1 are spread over 85 kJ mol(-1), and are all near thermochemical threshold. The corresponding onsets from 2 are in a 19 kJ mol(-1) range, and all except that of CH2=OH(+) are well above their thermochemical thresholds. Each decomposition of 3 occurs over a broad energy range (> 214 kJ mol(-1)), This demonstrates that ion-permanent dipole complexes can be significant intermediates over a much wider energy range than ion-induced dipole complexes can be. H-exchange between partners in the complexes appears to be much faster than exchange by conventional interconversions of the alcohol molecular ions with their distonic isomers. The onsets for water elimination from 1 and 2 are below the onsets for the complex-mediated processes, demonstrating that the latter are not necessarily the lowest energy decompositions of a given ion when the neutral partner in the complex is polar.

A photoionization study of the ion-neutral complexes CH3CH (+)CH 3 (·) CH 2CH 3] and CH 3CH 2CH (+)CH 3 (·) CH 3 in the gas phase: Formation, H-transfer and C-C bond formation between partners, and channeling of energy into dissociation.

Photoionization mass spectrometry was used to investigate the dynamics of ion-neutral complex-mediated dissociations of the n-pentane ion (1). Reinterpretation of previous data demonstrates that a fraction of ions 1 isomerizes to the 2-methylbutane ion (2) through the complex CH3CH(+)CH 3 (·) CH2CH3 (3), but not through CH3CH(+)CH2CH 3 (·) CH3 (4). The appearance energy for C3Hin 7 (+) formation from 1 is 66 kJ mol(-1) below that expected for the formation of n-C3H 7 (+) and just above that expected for formation of i-C3H 7 (+) . This demonstrates that the H shift that isomerizes C3H 7 (+) is synchronized with bond cleavage at the threshold for dissociation to that product. It is suggested that ions that contain n-alkyl chains generally dissociate directly to more stable rearranged carbenium ions. Ethane elimination from 3 is estimated to be about seven times more frequent than is C-C bond formation between the partners in that complex to form 2, which demonstrates a substantial preference in 3 for H abstraction over C-C bond formation. In 1 → CH3CH(+)CH2CH3 + CH3 by direct cleavage of the C1-C2 bond, the fragments part rapidly enough to prevent any reaction between them. However, 1 → 2 → 4 → C4H 8 (+) + CH4 occurs in this same energy range. Thus some of the potential energy made available by the isomerization of n-C4H9 in 1 is specifically channeled into the coordinate for dissociation. In contrast, analogous formation of 3 by 1 → 3 is predominantly followed by reaction between the electrostatically bound partners.

Size effects in ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers.

The effects of the size of the ionic and neutral partners on ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers were determined by obtaining metastable decomposition spectra and photoionization ionization efficiency curves. Increasing the size of the ionic partner decreases the competitiveness of alkane elimination with alkyl loss. This is attributed to decreasing attraction between the partners with increasing distance between the neutral partner and the center of charge in the associated ion. Increasing the size of the neutral partner lowers the threshold for alkane elimination relative to that for simple dissociation when the first threshold is above ΔHf(products). This is attributed to increasing attraction between the partners with increasing polarizability of the radical in the complex. Adding a CH2 to the radical in a complex seems to increase the attraction between the partners by about 24 kJ mol(-1).

A new method of preparation of segmental pancreatic grafts for transplantation: trials in dogs and in man.

A new method of eliminating the exocrine function of the pancreas by obstruction of pancreatic duct with neoprene was investigated in dogs and applied to three cases of human segmental pancreatic transplantation. Neoprene is a liquid synthetic rubber which flocculates with changes in pH. In animals, progressive fibrosis of the pancreatic tissue occurs after injection of neoprene in the main pancreatic duct, leaving islets well vascularized and functioning for prolonged periods. Using this technique, three severely diabetic patients received a cadaver segmental pancreatic allograft. Blood sugar returned to normal levels within the first hours or days after operation. All three grafts continue to function 1.5, 2, and 8 months, respectively, following transplantation. If these results are confirmed by further clinical experience, this method may be of considerable assistance in the treatment of severe diabetes by pancreatic transplantation.

Thoracic duct drainage and antilymphocyte globulin for renal transplantation in man.

Thoracic duct drainage resulting in a lymphocyte depletion of more than 20 x 10(9) cells was performed during the three months prior to transplantation in 37 patients. Results obtained in this group of patients were compared to those in transplant recipients similarly treated, over the same period, but not subjected to thoracic duct drainage. Both groups received comparable doses of antilymphocyte globulins, azathioprine and corticosteroids. No clear-cut difference in transplantation outcome was found when recipients of kidneys from related living donors (whether HLA identical or HLA haploidentical) were considered. By contrast, an improved transplant survival and a decreased incidence of rejection crises were observed in recipients of kidneys from cadaver donors when a thoracic duct drainage was performed prior to transplantation. The immunosuppressive effect of thoracic duct drainage, probably enhanced by antilymphocyte globulin treatment, is therefore a valuable adjunct to more conventional methods of pretreating human cadaveric transplant recipients.

Clinical experience with renal and neoprene-injected segmental pancreatic allografts in man.

We describe 22 clinical cases of segmental pancreatic grafts that were prepared with neoprene injection in the pancreatic duct. Complete correction of the diabetes is obtained during the period of function of the graft. The surgical procedure is a safe one and does not lead to a higher surgical risk than the usual kidney transplantation. Progress should be made by early detection and effective treatment of the pancreatic graft rejection. Corticoids should be avoided to suppress the diabetogenic effect. Cyclosporine A will probably be the immunosuppressive of choice.

Theoretical study of deprotonated glucopyranosyl disaccharide fragmentation.

Molecular orbital calculations were used to investigate the fragmentation of deprotonated glucopyranosyl disaccharides. Based on data from collisional activation and isotopic labeling experiments, fragmentation mechanisms are proposed, with calculated transition states being used to study the energetics of fragmentation. The calculations suggest that deprotonation at the C(2) hydroxyl of the non-reducing ring, following ring opening, may be important for disaccharide fragmentation. It is also shown that the stereochemistry at the 2-position of the non-reducing ring may have a significant effect on disaccharide fragmentation, particularly with regard to determination of the anomeric configuration.

New method for the specific clearance of antibodies using antigens linked to a collagen film.

A new type of immunoadsorbent, derived from a commercial haemodialysis module, has been designed. The dialysis membranes were replaced by bovine collagen membranes on which a given antigen had been linked by covalent binding. First, these membranes were tested in vitro: they were placed in contact with a given volume and concentration of antiserum to define their capacity to retain antibodies. Second, they were stacked in a modified haemodialyzer for antibody extraction ex vivo in dogs: the blood of immunized animals was passed over the immunoadsorbent and recirculated after either partial or total removal of antibodies. The degree of purification is related to the area of the membranes used and to the volume of blood to be purified.

Pharmacokinetics and bioavailability of pyridinol carbamate in humans.

The pharmacokinetics of two pyridinol carbamate formulations were studied after a single oral administration in 10 healthy volunteers. An open one-compartment model described the evolution of plasma concentrations as a function of time. Pyridinol carbamate was rapidly absorbed (mean lag time from 0.36 to 0.38 hr). Its elimination half-life ranged from 3.3 to 7.9 hr. The two formulations were bioequivalent.

Is serum creatinine a reliable expression of an adequate cyclosporine immunosuppression?

In 13 renal transplant patients with an excellent graft function, but concomitant abnormal T6 CsA plasma levels (CsA plasma level, 6 hours after oral administration of the drug), dose adjustments of CsA were performed until a normal T6 was achieved. A significant decrease of serum creatinine values was obtained after dose modification. Prophylactic monitoring of CsA immunosuppression by T6 could be a means of avoiding nephrotoxicity or undertreatment in patients with acceptable serum creatinine levels and unsuspected drug related renal dysfunction.