Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.     

NMR structure and mutagenesis of the FADD (Mort1) death-effector domain

When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity.     

Clinical applications of fundus reflection densitometry

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.     

Treatment of perianal fistulas with ND:YAG laser--results in twenty cases

Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs.     

Ferritin in cultured human cytotrophoblasts: synthesis and subunit distribution

The present study aims at the role of ferritin in the regulation of syncytiotrophoblast free iron levels. The differentiated cytotrophoblast cell in culture is used as a model for this maternal-fetal interface. Cytotrophoblast cells isolated from term placentae are cultured in iron-poor (Medium 199), iron-depleted [desferrioxamine(DFO)] and iron-supplemented [diferric transferrin (hTF-2Fe), ferric ammonium citrate (FAC)] medium. Distribution and de novo synthesis of isoferritins is studied, together with the cellular iron concentration and the ferritin iron saturation. Compared to ferritin isolated from total placenta, ferritin obtained from villous tissue is enriched with acidic isoforms. This observation is in agreement with measured light (L) to heavy (H) subunit ratios < 1 of de novo synthesized ferritin in cultured cytotrophoblast cells. Neither iron-poor culture medium, nor hTf-2Fe supplemented medium affects the cellular iron or ferritin concentration. FAC increased the cellular ferritin iron saturation and (by synthesis) the acidic isoferritin concentrations. The results strongly suggest, that the term syncytiotrophoblast is able to balance transferrin-mediated iron uptake and iron release. In case of FAC supplementation, the syncytiotrophoblast is unable to keep intracellular iron low, and ferritin synthesis is stimulated. The predominance of acidic ferritins and the preferential synthesis of H subunits can be functionally explained by the established fact that iron incorporation in acidic ferritins is faster due to the presence of ferroxidase centres. Damage by free iron catalysed hydroxyl radical formation is therefore minimized.     

Residues Val254, His256, and Phe259 of the angiotensin II AT1 receptor are not involved in ligand binding but participate in signal transduction

The role of the external third of helix VI of the angiotensin II (AII) AT1 receptor for the interaction with its ligand and for the subsequent signal transduction was investigated by individually replacing residues 252-256 by Ala, and residues 259 or 261 by Tyr, and permanently transfecting the resulting mutants to Chinese hamster ovary (CHO) cells. Binding experiments showed no great changes in affinity of any of the mutants for AII, [Sar1]-AII, or [Sar1, Leu8]-AII, but the affinity for the nonpeptide antagonist DuP753 was significantly decreased. The inositol phosphate response to AII was remarkably decreased in mutants V254A, H256A, and F259Y. These results indicate that AT1 residues Val254, His256, and Phe259 are not involved in ligand binding but participate in signal transduction. Based in these results and in others from the literature, it is suggested that, in addition to the His256 imidazole ring, the Phe259 aromatic ring interacts with the AII's Phe8, thus contributing to the signal-triggering mechanism.     

A histological and histomorphometrical evaluation of screw-type calciumphosphate (Ca-P) coated implants; an in vivo experiment in maxillary cancellous bone of goats

The bone response to different calcium phosphate (Ca-P) coated implants was evaluated in a goat animal model. Two types of plasma spray coatings were applied to a commercially pure titanium (cpTi) tapered, conical screw-design implant (BioComp^®); hydroxyapatite (HA-PS) and a dual coating, consisting of FA and HA (FA/HA-PS). In addition an amorphous RF magnetron sputter coating (Ca-P-a) and uncoated implants were investigated. Forty-eight implants were inserted in the maxilla of 12 adult female goats. After implantation periods of 3 and 6 months, the bone implant interface was evaluated histologically and histomorphometrically. After both implantation periods all plasma spray coated implants were maintained. On the other hand three Ca-P-a and two cpTi implants were lost. Histological examination revealed a better bone response to both plasma spray coated implants. Histomorphometrical evaluation confirmed this finding. At 3 and 6 months significantly higher percentages of bone contact (p<0.001, ANOVA) were measured for both plasma spray coated implants than for the cpTi and Ca-P-a implants, while no significant difference (p<0.05) existed between both implantation periods. Degradation of both plasma spray coatings was observed. Supported by the results, it is concluded that, although Ca-P coatings can improve the performance of dental implants, the presence of a Ca-P coating is not the only important factor for bone healing around implants placed in low density trabecular bone.     

Alterations of pH in response to increased dietary protein in cattle are unique to the uterus

This study was undertaken with two objectives: 1) to determine whether the effect of excess dietary protein on intrauterine pH in cattle is specific to the uterus or manifested in other bodily fluids and 2) to determine whether the effect of excess ruminally degradable protein on uterine pH can be ameliorated by substitution with a less-degradable protein source. Thirty-six Holstein cows in early lactation were fed isoenergetic total mixed rations that either 1) met undegradable intake protein (UIP) and degradable intake protein (DIP) requirements (Balanced), 2) met DIP requirements and exceeded UIP requirements by 25% (High UIP), or 3) met UIP requirements and exceeded DIP requirements by 25% (High DIP). After diets had been fed > or = 2 wk, uterine, blood, salivary, and urinary pH and plasma urea nitrogen were determined at estrus (d 0) and d 7. Plasma urea nitrogen (mg/dL) was not different between estrus and d 7 but was significantly affected by diet (Balanced, 16.1 +/- 2.3; High UIP, 19.2 +/- 1.6; High DIP, 22.3 +/- 2.6; P < .05). There was no effect of treatment on the pH of any fluid measured at estrus: intrauterine, blood, salivary, and urinary pH averaged 6.84 +/- .05, 7.39 +/- .01, 8.30 +/- .05, and 8.15 +/- .05, respectively. In contrast, on d 7, uterine pH was significantly lower in both high-protein groups, regardless of protein degradability (Balanced, 7.13 +/- .05; UIP, 6.95 +/- .04; DIP, 6.85 +/- .05; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)