Modeling methodologies developed for studying pharmacokinetic(PK)/pharmacodynamic(PD) processes confront many challenges related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves. Bayesian methods have provided a framework for PK/PD modeling and drug development that can address some of the above-mentioned challenges. This paper presents two illustrations of the application of Bayesian methods: the first involves a population modeling study of the cellular kinetics of the antiretroviral compound Lamivudine in the PBMCs of HIV-1 infected adolescents; the second uses a population mixture modeling approach to identifying hidden subpopulations that can not be identified by available measured covariates.

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Adolescent ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Child ; Child, Preschool ; Emergency Medical Services ; Female ; Humans ; Infant ; Male ; Prognosis ; Tachycardia, Ventricular ; complications ; pathology ; therapy ; Treatment Outcome

Animals ; Bone and Bones ; drug effects ; Dental Cements ; chemistry ; pharmacology ; Rats ; Tooth ; drug effects

OBJECTIVETo validate the previous anatomic study result about angle nerve of facial nerve through 3-dimensional (3-D) visualization technique, so as to provide theory basis for clinic treatment of nerve loss.

METHODThe full-thickness soft tissue at internal side of inner canthus was harvested from adult cadaveric head. The skin was 3 cm in length and 1 cm in width, with 2 parallel cut lines as location markers. The specimen was sliced continuously into 120 slices, with 10 microm in thickness for every slice, 0.25 mm apart. The slices underwent HE staining and 2-D digital image was gained by high resolution scanner. Then 3-D reconstruction was performed.

RESULTS(1) It showed the 3-D structures and routes of angle nerve, as well as the relationship between angle nerve and angle arteriovenous. All the reconstructed structures can be displayed together or separately, also from any angles. (2) It confirmed the accuracy of microscopic anatomy study about angle nerve. (3) The 3-D reconstruction of angle nerve, as well as the surrounding structure could be very useful for clinical application.

CONCLUSIONBased on the histologic study and computer technology, the 3-D reconstruction of angle nerve could provide accurate basis for the feasibility of clinic treatment of angle nerve loss.

Adult ; Facial Nerve ; anatomy & histology ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Visible Human Projects

OBJECTIVETo discuss the midface aging mechanism through anatomic study of malar fat pad.

METHODS10 fresh adult cadaveric heads (20 sides) fixed by vascular perfusion of formalin were used for anatomic study with microsurgery technique under microscope. The midfacial ligament and connective tissue between skin and subcutaneous fat were observed carefully in different parts of midface. The location, shape and extent of malar fat pad was also recorded and photographed.

RESULTSThe malar fat pad has a triangle shape. The bottom is a curve along the orbicularis retaining ligament at the lower eyelid. The fat pad is extended internally to the nasolabial fold and labiomandibular fold, externally from the major zygomatic muscle end point at the malar surface to the angulus oris and submandibular edge. (2) The malar fat pad is composed of meshed fibrous tissue, with big fat particles in it. It becomes tight when being stretched in horizontal direction along nasolabial fold and loosen when being stretched in vertical direction. (3) There is tight connection between skin and fat pad, which is divided into four areas as I, II, III, IV. The areas I, II, III are strip-shaped parelled to the nasolabial fold. The area IV is a irregular quadrilateral. (4) There are six fixation ligaments between malar fat pad and deep tissue: orbicularis retaining ligament upper layer of lower eyelid, orbicularis retaining ligament substratum of lower eyelid, zygomaticus ligament, zygomatic cutaneous ligament, zygomatic cutaneous ligament substratum, platysma There are four closely connected areas cutaneous forward ligament, cheek maxilla ligament.

CONCLUSIONSbetween the facial skin and malar fat pad which makes malar fat pad and skin keep relatively consistent. The malar fat pad moving down mainly resulted from slack of ligaments support which is one of the reasons for aging face.

Adipose Tissue ; anatomy & histology ; physiology ; Cadaver ; Cheek ; Eyelids ; anatomy & histology ; physiology ; Face ; anatomy & histology ; physiology ; Facial Muscles ; anatomy & histology ; physiology ; Head ; Humans ; Ligaments ; anatomy & histology ; physiology ; Lip ; anatomy & histology ; physiology ; Skin ; anatomy & histology ; Skin Aging ; pathology ; physiology

Background and purpose:Cyclooxygenase-2 (Cyclooxygenase-2,COX-2) is an important rate-limiting enzyme that is responsible for transformation of arachidonic acid into prostaglandins(PGs).Although Helicobacter pylori(Hp) infection-induced gastric over-expression of COX-2 (COX-2) is an important factor of gastric cancer,the mechanism of COX-2 expression in gastric mucosa cells infected with Hp is still not clear.Our study was to reveal the effect of Hp on expression of COX-2(cyclooxygenase-2),the impact of p38MAPK signaling pathway in human gastric epithelial cancer cells line MKN45,and to investigate the potential mechanisms of expression of COX-2. Methods:The expression of COX-2 mRNA infection by standard Hp NCTC11637 in human gastric epithelial cancer cells line MKN45 was evaluated by real-time fluorogenic quantitative polymerase chain reaction (RFQ-PCR).The effect of infection by Hp on COX-2 expression,activation of p38MAPK and its downstream of the ATF-2 was assayed by Western blot.Results:The expression of COX-2 mRNA in MKN45 cells infected by Hp compared with control group,COX-2 mRNA had 3 fold,7.2 fold,5.1 fold,4.3 fold up-regulation after 3 hrs,6 hrs,9 hrs,12 hrs,respectively. COX-2 mRNA expression in each time group was significantly higher than that in the control group(P

OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania. METHODS: Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA. RESULTS: The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05). CONCLUSION Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.
Aggression/drug effects* ; Antipsychotic Agents/therapeutic use* ; Biomarkers/blood* ; Bipolar Disorder/drug therapy* ; Case-Control Studies ; Diagnostic and Statistical Manual of Mental Disorders ; Double-Blind Method ; Humans ; Interleukin-17/metabolism* ; Lithium Compounds/therapeutic use* ; Quetiapine Fumarate/therapeutic use* ; Treatment Outcome

OBJECTIVETo study the anatomy of angular nerve (AN), so as to provide safe approach for the denervation surgery of corrugator supercilii, depressor supercilii and procerus.

METHODS10 fresh cadaver (20 sides)were perfused and fixed with formalin. Dissection was performed in the 10 x operating microscope. The plexus of the zygomatic branch and the buccal branch were detected to confirm the AN. The relationship of AN with the surrounding blood vessels was observed. We tracked AN until it entered corrugator supercilii, depressor supercilii and procerus.

RESULTS(1) AN was classified into I, II, III type according to its formation pattern. Type I (20%, 4/20 sides) AN is single, which is mainly from the plexus of buccal branch plus the zygomatic branch from the orbicularis oculi muscle. In type II (20%, 4/20 sides), the single AN was formed by buccal branch plexus and zygomatic branch plexus in the "Four Muscle Gap". In type III (60%, 12/20 sides), the AN had two branches in the "Four Muscle Gap". (2) The three types AN passed inferior to the support ligament at the suborbital part, and then transversed medial to the support ligament at the medial canthus, along the vessels of medial canthus. (3) The branch of AN enters the depressor supercilii or procerus 2.19 to 4.28 mm above the medial canthus ligament. The backward branch enters the levator labii superioris alaeque nasi 6.89 to 9.38 mm below the medial canthus ligament.

CONCLUSIONSThe approach of denervation surgery for AN should be performed medial to the support ligation, between 2.19 mm above the medial canthus and 6.89 mm below the medial canthus.

Adult ; Cadaver ; Denervation ; Facial Muscles ; innervation ; Facial Nerve ; anatomy & histology ; surgery ; Female ; Humans ; Male