Tea catechins' affinity for human cannabinoid receptors.

Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.

Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1.

BACKGROUND AND PURPOSE: Dietary anthocyanins hold great promise in the prevention of chronic disease but factors affecting their bioavailability remain poorly defined. Specifically, the role played by transport mechanisms at the intestinal and blood-brain barriers (BBB) is currently unknown. EXPERIMENTAL APPROACH: In the present study, 16 anthocyanins and anthocyanidins were exposed to the human efflux transporters multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), using dye efflux, ATPase and, for BCRP, vesicular transport assays. KEY RESULTS: All test compounds interacted with the BCRP transporter in vitro. Of these, seven emerged as potential BCRP substrates (malvidin, petunidin, malvidin-3-galactoside, malvidin-3,5-diglucoside, cyanidin-3-galactoside, peonidin-3-glucoside, cyanidin-3-glucoside) and 12 as potential inhibitors of BCRP (cyanidin, peonidin, cyanidin-3,5-diglucoside, malvidin, pelargonidin, delphinidin, petunidin, delphinidin-3-glucoside, cyanidin-3-rutinoside, malvidin-3-glucoside, pelargonidin-3,5-diglucoside, malvidin-3-galactoside). Malvidin, malvidin-3-galactoside and petunidin exhibited bimodal activities serving as BCRP substrates at low concentrations and, at higher concentrations, as BCRP inhibitors. Effects on MDR1, in contrast, were weak. Only aglycones exerted mild inhibitory activity. CONCLUSIONS AND IMPLICATIONS: Although the anthocyanidins under study may alter pharmacokinetics of drugs that are BCRP substrates, they are less likely to interfere with activities of MDR1 substrates. The present data suggest that several anthocyanins and anthocyanidins may be actively transported out of intestinal tissues and endothelia, limiting their bioavailability in plasma and brain.

[Retrospective analysis of healing problems after reamed and unreamed nailing of femoral shaft fractures]. / Retrospektive Analyse der Heilungsstörungen nach aufgebohrter und unaufgebohrter Nagelung von Femurschaftfrakturen.

168 fractures of the femoral shaft treated by intramedullary nailing were analyzed retrospectively. From 1986-1992 116 fractures had been treated with the reamed AO universal nail (RFN) and from 1993-1996 52 fractures with the AO unreamed femoral nail (UFN). In 24% of the RFN-group and in 2% of the UFN-group (p < 0.0001) open reduction of the fracture had been necessary. The time to radiological consolidation was similar in both groups (18.1 weeks +/- 6.1 vs. 18.3 weeks +/- 5.7, [mean +/- SD]). Delayed unions were less frequent in the RFN-group than in the UFN-group (3% vs. 13%, p = 0.01). Non-unions occurred in the RFN-group in 4%, in the UFN-group in 8%, the difference is not statistically significant (p = 0.46). Fractures with impaired consolidation (delayed-unions and non-unions) in the RFN group were distributed randomly along the femoral diaphysis, whereas all 11 fractures with retarded healing in the UFN group were short transverse or oblique fractures localized immediately distal to the femoral isthmus. We believe that there is mainly a mechanical reason for this phenomen, in addition to fracture type and fracture localization the (insufficient) length of the unreamed nails might have impaired stability further. The different factors should be investigated in larger series. As a consequence we now treat transverse and short oblique fractures of diaphyseal femoral fractures distal to the femoral isthmus with a RFN whereas in other types and localizations of diaphyseal femoral fractures we continue to use the UFN with special attention to maximal nail diameter and length.

[MR-Arthrography with radial sequences for visualization of early hip pathology not visible on plain radiographs]. / Arthro-MRI mit radiärer Schnittsequenz zur Darstellung der präradiologischen Hüftpathologie.

AIM: We wanted to improve MRI visualization of early hip pathology invisible on plain radiographs. METHOD: An MR arthrography of the hip with radial sequences is described. The standard MR technique is improved by 1) using a small flexible surface coil to show selectively the hip joint to be examined, 2) application of gadolinium intra-articularly and 3) by radial imaging sequences perpendicular to the true plane of the acetabulum. CONCLUSION: By this technique it is possible to achieve an undistorted image of each aspect of the acetabular rim. Regions of special interest can be defined and their pathologies possibly related to morphologies of the proximal end of the femur.

[Inadequate detectability of early stages of coxarthrosis with conventional roentgen images]. / Mangelhafte Erfassbarkeit von Frühstadien der Coxarthrose mit konventionellen Röntgenbildern.

AIM: The study was undertaken to determine the value of standard radiographs in the early stages of osteoarthritis. METHODS: Standard radiographs and arthro-MRI's from thirty hips operated on for early arthrosis (age 25-57 years) were independently analyzed by two orthopaedic surgeons and one radiologist blinded from the intra-operative findings. The radiographs were read on two occasions two months apart. The radiographic findings were then compared to the intra-operative findings. RESULTS: Intra-operatively, all cases had a labral lesion and, in all but three of the cases, there was a major acetabular cartilage lesion. Each investigator diagnosed all of the labral and/or cartilage lesions on the arthro-MRI. However, on average, the investigators judged 20% (10-35%) of the hips to be normal on the standard radiographs. The probability of detecting an abnormal hip joint was statistically significantly better with arthro-MRI in four of six readings (p < 0.05) and there was a trend in favor of the arthro-MRI in the other two readings (p < 0.1). Intra-observer agreement when using the Tönnis classification of arthrosis on standard radiographs was 0.26 (-0.1-0.62), 0.69 (0.42-0.96) and 0.83 (0.53-1) [kappa-statistic, (95% confidence interval)]. The interobserver agreement was 0.24 (-0.07-0.55). CONCLUSION: Plain radiographs in the early stages of osteoarthrosis of the hip are neither reliable nor valid to diagnose the onset of disease. Therefore, in the case of a normal radiograph and clinical suspicion of arthrosis, a "normal" radiograph does not exclude the diagnosis and an artho-MRI should be obtained for further evaluation.

[Blood loss in total hip prosthesis implantation: lateral versus supine position]. / Blutverlust bei Hüfttotalprothesenimplantationen: Seitenlage versus Rückenlage.

We performed a prospective randomized study to determine blood loss differences between supine or lateral patient position, during surgery in elective total hip replacement. Between January and October 1996, 64 consecutive cases of total hip replacements were randomly scheduled for a procedure either in the supine or in the lateral position. Of the 56 cases evaluated, 29 were operated in the supine position (SP) and 27 in the lateral position (LP). The standardized implantations were performed without cement and the blood loss was measured. The calculated loss of Hb on the day of operation was 235 g Hb +/- 17 (mean +/- s.e.) in the SP group and 177 g Hb +/- 14 in the LP group, respectively, (unpaired t-test p = 0.01). The calculated loss of Hb after five postoperative days was 227 g Hb +/- 24 (mean +/- s.e.) in the SP group and 179 g Hb +/- 24 in the LP group, respectively, p < 0.2. The net loss of Hb after five postoperative days was calculated by subtracting all perioperative blood substitutions (Cellsaver, autologous and homologous blood) resulting in 340 g Hb +/- 21 (mean +/- s.e.) in the SP group and 272 g Hb +/- 21 in the LP group, respectively, p = 0.02. The blood loss in primary cementless total hip replacement surgery can be significantly reduced by performing the procedure in the lateral position compared to that in the supine position. The blood loss is limited to the day of operation, as indicated by the stable Hb-levels thereafter.

[Acute liver and kidney failure following sorbitol infusion in a 28-year-old patient with undiagnosed fructose intolerance]. / Akutes Leber- und Nierenversagen nach Sorbitinfusion bei 28jährigem Patienten mit undiagnostizierter Fruktoseintoleranz.

In connection with nephrectomy fatal liver and renal failure occurred after infusion of 50 g sorbitol in a 28 years old patient with undiagnosed fructose intolerance. A marked hypoglycemia and lactacidosis, an increase in uric acid, an acute liver failure with breakdown of excretory and synthetic function and disorder of hemostasis were typical of fructose/sorbitol infusion in hereditary fructose intolerance. Under adequate diet, as indicated in our case, HFI could be undiagnosed up to adult age. Therefore, fructose intolerance should be excluded by anamnesis before infusion of fructose/sorbitol. In unknown anamnesis (unconsciousness) fructose/sorbitol containing infusions should not be used. Fructose/sorbitol containing infusions should not be given routinely, but only with certain indication.

Radiation-induced thymine base damage and its excision repair in active and inactive chromatin of HeLa cells.

The extent of production and excision repair of 5,6-dihydroxydihydrothymine type base (t') damage was determined in transcriptionally active and inactive chromatin of HeLa cells after exposure to 6.8 MeV electrons. It was observed that not only the yield but also rate of repair of t' products was greater in the active chromatin compared to the inactive chromatin of HeLa cells. The results strongly indicate that the conformation of chromatin is an important factor in determining the sensitivity to radiation damage and accessibility to enzymes required for repair of such damage.

Age associated alteration in DNA damage and repair capacity in Turbatrix aceti exposed to ionizing radiation.

Excision repair capacity was measured in young and old Turbatrix aceti (phylum Nematoda) following exposure to ionizing radiation. Both repair synthesis and removal of 5,6-dihydroxydihydrothymine type (glycol) base damage were quantitated. At least two-fold higher glycol levels were produced in the DNA of young than of old nematodes for the same radiation dose. Young worms also excised glycol damage more rapidly and completely than old worms. Both peak repair synthesis activity and completion of repair synthesis occurred at earlier times during post-irradiation incubation in young nematodes. The data indicate there is a significant age-associated difference in both the incidence and removal of ionizing radiation damage in T. aceti which is used as a model of the ageing process.

Age-related changes in the excision repair capacity of Turbatrix aceti.

Excision repair capacity was measured in the free-living nematode Turbatrix aceti, a model aging system. Excision repair was assessed by both repair synthesis activity and the actual removal of pyrimidine dimers from the genome. The young organisms removed lesions more rapidly and completely than the old for all fluences tested. Repair synthesis began and peaked earlier for young nematodes than old. The data consistently indicated a decline in DNA excision repair capacity with age in the nematode.

Production and excision repair of cyclobutane-type pyrimidine dimers in the DNA of Turbatrix aceti.

The production and removal of 254 nm ultraviolet-induced pyrimidine dimers was measured in the DNA of the free-living nematode Turbatrix aceti. Approximately 0.0035 per cent pyrimidine dimers are produced per J/m2. Following a fluence of 100 Jm2, approximately 50 per cent of the dimeric photoproducts were excised within 60 min. The number of pyrimidine dimers excised did not change with increasing U.V. fluence, indicating saturation of the U.V. repair system in T. aceti. The results indicate a highly efficient and selective repair system in Turbatrix aceti for dimeric photoproducts.

Relationship between cytotoxicity and DNA damage in mammalian cells treated with anthracenedione derivatives.

The effects of two anthracenedione derivatives on in vitro cell survival and DNA of Chinese hamster ovary (CHO) cells were investigated. The two drugs studied were 1,4-dihydroxy-5,8-bis-(2-[2-hydroxyethyl)amino)ethylamino)-9,10-anthracenedione (DHAQ, NSC No. 279836) and 1,4-bis-(2-[2-hydroxyethyl)-amino)ethylamino)-9,10-anthracenedione (HAQ, NSC No. 287513). DHAQ was 100-fold more potent in reducing cell survival than HAQ. DNA strand breaks were assayed by alkaline elution. DHAQ (10 ng/ml) caused more strand breakage than 1000 ng/ml HAQ. This difference correlates well with their differences in ability to kill cells.

Effect of cordycepin(3'-deoxyadenosine) on excision repair of 5,6-dihydroxy-dihydrothymine-type products from the DNA of Micrococcus radiodurans.

Cordycepin(3'-deoxyadenosine), a nucleoside analog, has been shown to enhance radiation-induced cell killing. In an effort to elucidate the possible mechanism for enhancement of cell killing, the effect of cordycepin on the excision repair of radiation-induced 5,6-dihydroxy-dihydrothymine-type (t') products from the DNA of wild type Micrococcus radiodurans was investigated. The capacity of M. radiodurans to excise nondimeric (t') products from its DNA was significantly impaired after cordycepin treatment. The results suggest that the increased radiation sensitivity of cordycepin-treated cells could be due to alterations in cellular processes that repair DNA damage.