[Reconsideration of the indications for unicompartmental knee arthroplasty].

Unicompartmental knee arthroplasty (UKA), a procedure that has gradually emerged in recent years, is considered an effective treatment for resolving knee pain and restoring good function due to its significant clinical advantages. In the 1980s, Kozinn and Scott proposed the classic indications as selection criteria to identify ideal candidates for UKA. However, as treatment concepts, surgical instruments, surgical techniques, and prosthesis designs for this disease have improved, these indications proposed more than 30 years ago appear too limited, leading to some limitations in the widespread use of UKA. Specifically, surgeons have offered new perspectives on issues related to obesity, age, patellofemoral arthritis, severe varus deformity of the knee, anterior cruciate ligament deficiency, flexion contracture, failed high tibial osteotomy and post-traumatic arthritis. For this reason, this article will briefly discuss modern perspectives involving the indications for UKA based on current evidence with the aim of providing a reference for the reader.

[Lateral unicompartmental knee arthroplasty: challenges and hopes].

There is a low prevalence of osteoarthritis in the lateral compartment of the knee, but the overall number of domestic patients is large, and lateral unicompartmental arthroplasty (UKA) has good prospects.The unique anatomical structure and kinematic characteristics of the lateral compartment make the surgical operation more challenging.Traditional UKA patients have a high incidence of lower limb mal-alignment and poor prosthetic position, which leads to limit of their promotion and application.In recent years, with the development of treatment concepts, surgical techniques and materials, the survival time of UKA prosthesis has been continuously extended, and the clinical effect has been continuously optimized.Strictly grasp the surgical indications in radiology, anatomy and clinical manifestations, familiarize with the lateral compartment anatomy and biomechanical features, and master the technical details are the prerequisites and guarantees for the success of the lateral UKA.With the advancement of technology, minimal invasion, precision and individuation should be the goal pursued for lateral UKA surgery.

Polydatin alleviates osteoporosis by enhancing the osteogenic differentiation of osteoblasts.

OBJECTIVE: Osteoporosis is a severe degenerative chronic metabolic bone disease associated with high fracture risk. Polydatin (PD), a major bioactive component of Polygonum cuspidatum, has antioxidant and anti-inflammatory effects. This study investigated the anti-osteoporotic activity of PD in ovariectomized (OVX) mice and elucidated its underlying molecular mechanisms. SUBJECTS AND METHODS: An osteoporosis mouse model was established using OVX mice. OVX mice were then administered 10 or 40 mg/kg of PD for 60 days. Micro-CT and three-point bending tests were used to determine the therapeutic activities of PD in OVX mice. H&E staining was used to determine whether PD induced hepatorenal toxicity. In addition, the cellular and molecular mechanisms underlying the functionality of PD were elucidated. RESULTS: Micro-CT results showed that compared to control mice, the bone mass of OVX mice was significantly reduced due to estrogen deficiency; however, PD administration significantly elevated bone mass. Furthermore, PD substantially improved the trabecular microstructure parameters of the femur and enhanced bone strength compared with OVX mice. Hepatorenal toxicity was not observed in liver and kidney samples stained with H&E. PD significantly increased the proliferation of pre-osteoblast MC3T3-E1 cells and upregulated the expression of osteogenic differentiation markers compared to those in controls, as determined by qRT-PCR and western blotting. CONCLUSIONS: PD exerted a significant anti-osteoporotic effect in OVX mice by promoting osteogenesis. PD has great potential as a therapeutic option for osteoporosis.

Two microtubule-associated proteins required for anaphase spindle movement in Saccharomyces cerevisiae.

In many eucaryotic cells, the midzone of the mitotic spindle forms a distinct structure containing a specific set of proteins. We have isolated ASE1, a gene encoding a component of the Saccharomyces cerevisiae spindle midzone. Strains lacking both ASE1 and BIK1, which encodes an S. cerevisiae microtubule-associated protein, are inviable. The analysis of the phenotype of a bik1 ase1 conditional double mutant suggests that BIK1 and ASE1 are not required for the assembly of a bipolar spindle, but are essential for anaphase spindle elongation. The steady-state levels of Ase1p are regulated in a manner that is consistent with a function during anaphase: they are low in G1, accumulate to maximal levels after S phase and then drop as cells exit mitosis. Components of the spindle midzone may therefore be required in vivo for anaphase spindle movement. Additionally, anaphase spindle movement may depend on a dedicated set of genes whose expression is induced at G2/M.

Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease.

Caveolae are 50-100-nm membrane microdomains that represent a subcompartment of the plasma membrane. Previous morphological studies have implicated caveolae in (a) the transcytosis of macromolecules (including LDL and modified LDLs) across capillary endothelial cells, (b) the uptake of small molecules via a process termed potocytosis involving GPI-linked receptor molecules and an unknown anion transport protein, (c) interactions with the actin-based cytoskeleton, and (d) the compartmentalization of certain signaling molecules, including G-protein coupled receptors. Caveolin, a 22-kD integral membrane protein, is an important structural component of caveolae that was first identified as a major v-Src substrate in Rous sarcoma virus transformed cells. This finding initially suggested a relationship between caveolin, transmembrane signaling, and cellular transformation. We have recently developed a procedure for isolating caveolin-rich membrane domains from cultured cells. To facilitate biochemical manipulations, we have applied this procedure to lung tissue--an endothelial and caveolin-rich source-allowing large scale preparation of these complexes. These membrane domains retain approximately 85% of caveolin and approximately 55% of a GPI-linked marker protein, while they exclude > or = 98% of integral plasma membrane protein markers and > or = 99.6% of other organelle-specific membrane markers tested. Characterization of these complexes by micro-sequencing and immuno-blotting reveals known receptors for modified forms of LDL (scavenger receptors: CD 36 and RAGE), multiple GPI-linked proteins, an anion transporter (plasma membrane porin), cytoskeletal elements, and cytoplasmic signaling molecules--including Src-like kinases, hetero-trimeric G-proteins, and three members of the Rap family of small GTPases (Rap 1--the Ras tumor suppressor protein, Rap 2, and TC21). At least a fraction of the actin in these complexes appeared monomeric (G-actin), suggesting that these domains could represent membrane bound sites for microfilament nucleation/assembly during signaling. Given that the majority of these proteins are known molecules, our current studies provide a systematic basis for evaluating these interactions in vivo.

Identification of I-plastin, a human fimbrin isoform expressed in intestine and kidney.

The complete cDNA sequence of human intestine-specific plastin (I-plastin) was determined from a clone derived by PCR. It consists of a 97-bp 5' untranslated region, a 1,887-bp coding region, and a 1,655-bp 3' untranslated region. The coding region predicts a 629-residue polypeptide whose sequence displays 86, 75, and 73% identities with chicken intestine fimbrin, human T-plastin, and human L-plastin, respectively. Recombinant I-plastin cross-linked actin filaments into bundles in the absence but not in the presence of calcium. The I-plastin gene was mapped by PCR to human chromosome 3; the L- and T-plastin genes were previously mapped to chromosomes 13 and X, respectively. I-plastin mRNA was detected in the small intestine, colon, and kidneys; relatively lower levels of expression were detected in the lungs and stomach. In contrast, L-plastin expression was restricted to the spleen and other lymph node-containing organs, while T-plastin was expressed in a variety of organs, including muscle, brain, uterus, and esophagus. In contrast to the situation for the intestine, high levels of L- and T-plastin mRNAs were detected in Caco-2, a human colon-derived cell line. Immunofluorescence microscopy detected I-plastin in the brush border of the small intestine and colon. These results identify I-plastin as the human homolog of chicken intestine fimbrin and as a third plastin isoform in humans.

Evaluation of mandibular contour in patients with significant facial asymmetry.

Most previous studies on facial asymmetry have not specifically differentiated mandible deviation from structural asymmetry of the mandible. The purpose of this study was to assess the symmetry of the mandible by examining its contour in a cohort of patients with significant facial asymmetry. Eleven cases of facial asymmetry with chin deviation ≥10mm were enrolled. A voxel-paired median plane (optimal symmetry plane, OSP) and two landmark-based median planes were generated. The OSP was created by computing the best pairing of the bony voxels on the two sides. One side of the mandibular contour was mirrored onto the other side using the test plane. The contour differences were measured by distance and by area ratio. They were examined both in frontal and frontal downward inclined view. The contour symmetry of the mandible was that revealed by the plane that presented the best symmetry. The results showed that the OSP worked best in bisecting the contour into two symmetrical halves. Contour analysis showed relatively small discrepancies between the two sides. In conclusion, the mandibles retained an acceptable contour symmetry despite the presence of significant mandibular deviations. It is suggested that proper mandibular alignment be the primary objective in the correction of facial asymmetry.

A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures.

Inner-city minority populations are high-risk groups for adverse birth outcomes and also more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia Center for Children's Environmental Health (CCCEH) is conducting a prospective cohort study of 700 northern Manhattan pregnant women and newborns to examine the effects of prenatal exposure to these common toxicants on fetal growth, early neurodevelopment, and respiratory health. This paper summarizes results of three published studies demonstrating the effects of prenatal ETS, PAH, and pesticides on birth outcomes and/or neurocognitive development [Perera FP, Rauh V, Whyatt RM, Tsai WY, Bernert JT, Tu YH, et al. Molecular evidence of an interaction between prenatal environment exposures on birth outcomes in a multiethnic population. Environ Health Perspect 2004;12:630-62; Rauh VA, Whyatt RM, Garfinkel R, Andrews H, Hoepner L, Reyes A, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol 2004;26:373-85; Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, et al. Prenatal insecticide exposures, birth weight and length among an urban minority cohort. Environ Health Perspect, in press]. To evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides, researchers analyzed questionnaire data, cord blood plasma (including biomarkers of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of PAHs). Self-reported ETS was associated with decreased head circumference (P = 0.04), and there was a significant interaction between ETS and adducts such that combined exposure had a significant multiplicative effect on birth weight (P = 0.04) and head circumference (P = 0.01) after adjusting for confounders. A second analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum material hardship (unmet basic needs in the areas of food, housing, and clothing) on 2-year cognitive development. Both exposures depressed cognitive development (P < 0.05), and there was a significant interaction such that children with exposure to both ETS and material hardship exhibited the greatest cognitive deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were inversely associated with birth weight and/or length (P < 0.05). These results underscore the importance of policies that reduce exposure to ETS, air pollution, and pesticides with potentially adverse effects on fetal growth and child neurodevelopment.

In vitro iontophoretic studies using a synthetic membrane.

In vitro iontophoretic administration of drugs through a microporous polyolefin membrane with hydrophilic urethane polymerfilled pores was done for the ionized drugs dexamethasone sodium phosphate, hydrocortisone sodium phosphate, and prednisolone sodium succinate, and for a nonionizable drug cortisone acetate. Currents between 0.2 and 0.8 mA were demonstrated to be effective in increasing the transmembrane transport rate compared with passive diffusion for all the ionizable drugs studied. However, these currents failed to show any significant effect on the transmembrane transport rate of the nonionizable drug, cortisone acetate. There was a good linear relationship between the applied current (I, mA) and the transmembrane transport rate (J, micrograms/mL) in the receptor cell for all the ionized drugs (J = 1.97I + 0.70 for dexamethasone sodium phosphate; J = 2.05I + 1.49 for hydrocortisone sodium succinate; J = 2.25I + 1.93 for prednisolone sodium succinate). This in vitro iontophoretic study demonstrated that electric fields interact more efficiently with charged than with uncharged molecules.

Degradation kinetics of phentolamine hydrochloride in solution.

The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determination for phentolamine hydrochloride was found to be 9.55 +/- 0.10 (n = 5) at 25 +/- 0.2 degrees C. This indicated the protonated form of phentolamine occurs in the pH range of this study. The pH-rate profile indicated a pH-independent region (pH 3.1-4.9) exists with a minimum rate around pH 2.1. The catalytic effect of acetate and phosphate buffer species is ordinary. The catalytic rate constants imposed by acetic acid, acetate ion, dihydrogen phosphate ion, and monohydrogen phosphate ion were determined to be 0.018, 0.362, 0.036, and 1.470 L mol-1 h-1, respectively. The salt effect in acetate and phosphate buffers followed the modified Debye-Huckel equation quite well. The ZAZB value obtained from the experiment closely predicts the charges of the reacting species. The apparent energy of activation was determined to be 19.72 kcal/mol for degradation of phentolamine hydrochloride in pH 3.1, 0.1 M acetate buffer solution at constant ionic strength (mu = 0.5). Irradiation with 254 nm UV light at 25 +/- 0.2 degrees C showed a ninefold increase in the degradation rate compared with the light-protected control. Propylene glycol had little or no effect on the degradation of phentolamine hydrochloride at 90 +/- 0.2 degrees C; however, polyethylene glycol 400 had a definite effect.

Iontophoresis of hydrocortisone across hairless mouse skin: investigation of skin alteration.

The effects of hydration, sodium dodecyl sulfate (SDS), and electric current on the permeability of hairless mouse skin was examined in vitro with a neutral solute, hydrocortisone, as a permeant. The study was carried out by pretreating the skin with (1) normal saline, (2) 0.06% SDS in 0.3% NaCl, (3) normal saline plus 0.5 mA anodic current, and (4) 0.06% SDS in 0.3% NaCl plus 0.5 mA anodic current for 8 h. The pretreated skin was then immediately used for passive or anodic transport of hydrocortisone. Results show that pretreatment of skin with either normal saline or 0.06% SDS resulted in a slightly increased passive penetration of hydrocortisone with a prolonged lag time, but did not significantly change the anodic transport of hydrocortisone. There was no significant difference between normal saline pretreatment and 0.06% SDS pretreatment, indicating that 0.06% SDS did not irreversibly alter the permeability of skin other than its hydration effect. Pretreatment of skin with current, and especially with current combined with 0.06% SDS, yielded a significant increase in both passive and anodic transport of hydrocortisone with reduced lag time, indicating that alteration of the skin structure had occurred. The reversibility of this alteration depends on the duration of exposure of the skin to the electric field. Short-term exposure (< 2 h) does not appear to change the permeability of skin in any significant way; long-term exposure may lead to slowly reversible or irreversible skin alteration.

Nefopam hydrochloride degradation kinetics in solution.

A stability-indicating reversed-phase high performance liquid chromatographic method was developed for the detection of nefopam hydrochloride and its degradation products under accelerated degradation conditions. The degradation kinetics of nefopam hydrochloride in aqueous solutions over a pH range of 1.18 to 9.94 at 90 +/- 0.2 degrees C was studied. The degradation of nefopam hydrochloride was found to follow apparent first-order kinetics. The pH-rate profile shows that maximum stability of nefopam hydrochloride was obtained at pH 5.2-5.4. No general acid or base catalysis from acetate, phosphate, or borate buffer species was observed. The catalytic rate constants on the protonated nefopam imposed by hydrogen ion and water was determined to be 7.16 X 10(-6) M-1 sec-1, and 4.54 X 10(-9) sec-1, respectively. The pKa of nefopam hydrochloride in aqueous solution was determined to be 8.98 +/- 0.33 (n = 3) at 25 +/- 0.2 degrees C by the spectrophotometric method. The catalytic rate constant of hydroxyl ion on the degradation of nefopam in either protonated or nonprotonated form was determined to be 6.63 X 10(-6) M-1 sec-1 and 4.06 X 10(-6) M-1 sec-1, respectively. A smaller effect of hydroxyl ion on the degradation of nonprotonated than on the degradation of protonated nefopam was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of trimethoprim in the rat.

The pharmacokinetics of trimethoprim was studied in male Sprague-Dawley rats following the intravenous administration of trimethoprim at a dose of 25 mg/kg. Plasma and tissue levels of trimethoprim, as a function of time, were determined by reversed-phase high-performance liquid chromatography. The disposition of trimethoprim was described by both a two-compartment open model with elimination from a central compartment and a noncompartmental method. For the compartmental analysis, the terminal elimination rate constant, elimination half-life, apparent volume of distribution in the central compartment, apparent volume of distribution in the central compartment based on the area under the plasma concentration-time curve, and volume of distribution at steady state, were determined to be 0.007 min-1, 99 min, 2059 mL/kg, 5729 mL/kg, and 2473 mL/kg, respectively. Noncompartmental pharmacokinetic parameters were obtained by the statistical moment theory. The estimates for mean residence time, clearance, and volume of distribution at steady state of trimethoprim were calculated to be 52 min, 40 mL.min-1kg-1, and 2097 mL, respectively. Tissue distribution of trimethoprim followed a biphasic phenomenon with a maximum concentration at 30 min for heart, lung, spleen, liver, kidney, seminal vesicles, and muscle, and at 45 min for testicles, 20 min for prostate gland, and less than 10 min for brain. The data show that compared with the plasma concentration, higher levels of trimethoprim were found in heart, lung, spleen, liver, kidney, prostate gland, and seminal vesicles; a similar concentration was found for muscle, but lower levels of trimethoprim were found for brain and testicles.

Effect of pH on the equilibrium dialysis of phenytoin suspension with and without enteral feeding formula.

Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5.(ABSTRACT TRUNCATED AT 250 WORDS)

[The protective effect of endogenous and exogenous somatostatin on monolayer cultured islet B cells damaged by streptozotocin].

Exogenous administration of somatostatin exerted a beneficial influence directly on monolayer cultured islet B cells damaged by streptozotocin (3.0 mmol/L). Six to twelve hours following the pretreatment with somatostatin of 0.025, 0.05 and 0.1 microgram/ml the number of viable cells was significantly increased from 41.13 +/- 0.65 x 10(4) cells/ml (STZ control) to 49.0 +/- 2.0, 53.0 +/- 1.33, 53.38 +/- 1.74 x 10(4) cells/ml, respectively. The ultrastructural appearance of the B cells indicated that with many vacuoles and granules occurred in the cytoplasma of these cells, normal organelles disappeared and the nuclei were obscure in structure. The pretreatment with somatostatin (0.1 microgram/ml) protected the B cells against streptozotocin, with mitochondria, Golgi's apparatus and granules in these cells intact. The destruction of B cells induced by streptozotocin was more severe after adding anti-somatostatin serum to neutralize the endogenous somatostatin in the culture, which was reversed by replenishment of somatostatin. Adding Ca2+ carrier A23187 did not change the protective effect of somatostatin, it seemed that there was no relationship between the protective effect of somatostatin and calcium mechanism.

[The increase of protein synthesis by zinc can resist the damage induced by streptozotocin on islet cells].

The beneficial effect of ZnCl2 on islet cells injured by streptozotocin was observed directly on the cultured cells and its possible mechanism was analysed. The results were as follows: (1) The number of viable cells in culture was reduced from 70 x 10(5)/ml to 43.93 +/- 1.16 x 10(5)/ml 12 hours after adding normal saline plus STZ (3.0 mmol/L), and this reduction could be alleviated by adding ZnCl2 (0.25, 0.5, 1.0 mmol/L) in varying amounts and a dose-response relationship was found. The number of viable cells was returned to 47.39 +/- 0.88 x 10(5)/ml, 58.06 +/- 2.29 x 10(5)/ml, and 67.72 +/- 1.48 x 10(5)/ml respectively in the culture with ZnCl2 of different levels. (2) The effect of ZnCl2 was reversed when cycloheximide (100 micrograms/ml), a protein synthesis inhibitor, was added into the cultural medium, and the number of viable cells was again decreased from 63.17 +/- 2.15 x 10(5)/ml to 45.77 +/- 0.76 x 10(5) ml. No obvious effect was observed when cycloheximide was given alone. (3) The experiment of 3H-leucine incorporation into islet cells showed that protein synthesis was increased slightly and insignificantly after adding ZnCl2 (1.0 mmol/L). However, there was a significant increase of protein synthesis in cells when ZnCl2 (1.0 mmol/L) was added with STZ (3.0 mmol/L). The results suggest that ZnCl2 has a protective effect on the damaged islet cells induced by STZ. The increase of protein synthesis may be one of the mechanisms involved in the action of ZnCl2, which strengthens the repairing ability of islet cells after injury.

Uptake of trimethoprim and metronidazole in the seminal vesicle: experimental study.

A rat model for determining drug levels in the seminal vesicle was developed. In separate studies, trimethoprim and metronidazole were injected intravenously into rats and assays of seminal vesicle, plasma, and prostate performed. Drug levels were detected early in both the seminal vesicle and prostate. This appears to be the first study to report drug levels in the seminal vesicle. Metronidazole levels in the seminal vesicle were very low and short lived.