Cholesterol: the good, the bad, and the ugly - therapeutic targets for the treatment of dyslipidemia

Maintaining cholesterol and triglyceride [TG] levels within healthy limits is critical for decreasing the risk of heart disease. Dyslipidemia refers to the abnormal levels of lipids in the blood, including low high-density lipoprotein cholesterol [HDL-C], also known as good cholesterol, high low-density lipoprotein cholesterol [LDL-C], also known as bad cholesterol, and/or high TG levels that contribute to the development and progression of atherosclerosis. In this article we reviewed some of the current therapeutic targets for the treatment of dyslipidemia, with a primary focus on endothelial lipase and lecithin cholesterol acyl transferase for raising HDL-C, and the proprotein convertase subtilisin-like kexin type 9 [PCSK9], microsomal triglyceride transfer protein, and the messenger RNA of apolipoprotein B for lowering LDL-C. In addition, we reviewed the role of apolipoprotein AI [apoAI] in raising HDL-C, where we discuss three apoAI-based drugs under development. These are its mutated dimer [apoAI-Milano], a complex with phospholipids, and a mimetic peptide. Atherosclerosis, mainly because of dyslipidemia, is a leading cause of cardiovascular disease. Regarding the title of this article, the 'good' refers to HDL-C, the 'bad' refers to LDL-C, and the 'ugly' refers to atherosclerosis

effect of a biplane symphyseal plate on rigid anterior segment internal fixation of the pelvic ring: a biomechanical study

An experimental study was conducted firstly to test the effect of a newly designed biplane symphyseal plate on rigid anterior segment internal fixation of the pelvic ring, and secondly to test its use in rotationally unstable fractures singly or combined with posterior internal fixation in vertically unstable fractures. The questions posed were: 1] How does the designed plate compare with a single 4.5mm reconstruction plate for anterior symphyseal fixation. 2] How do the anterior and posterior columns of the acetabulum, and the inferior pubic ramus behave in each situation of pelvic compression [anteroposterior or lateral] and shear. Six dry bone pelves were tested to failure after mounting them onto a universal hydraulic testing machine run in a displacement-controlled mode at a rate of 0.5mm/sec. Of the six specimens tested, three were fixed with a standard 4.5mm reconstruction plate, the other 3 were fixed with a biplane plate. Each of the 3 specimens was tested once for APC [anteroposterior compression], once for LC [lateral compression] and once for VS [vertical shear]. The end point of the test was either failure of bone in the form of a fracture or failure of the plate in the form of a screw or more backing out. Strain during loading was also measured using precision strain gauges. Data from the strain gauges were recorded on a computer through a scanner [System 5000/Model 5100 by Vishay company, USA]. The data were analyzed by recording the strain measured from each gauge against time, while the universal hydraulic testing machine applied APC [anteroposterior compression], LC [lateral compression] and VS [vertical shear] on the bony specimen. Data were analyzed using a special software for statistical analysis [SPSS program, version 8.0]. The pelvis fixed with our plate resisted failure in APC, LC and VS more than pelves fixed with a 4.5mm reconstruction plates. In this respect, our results concurred with those of others [9,11,12,15], but differed from other studies [10,14]. The strain gauge system helped us better define the distribution of stresses. Our plate was superior in resorbing tension off both anterior and posterior columns in APC and VS. Thus in both of these injuries it unloads posterior fixation devices, although in APC the inferior pubic ramus showed less compression but higher tension with our plate. In LC the tension in the posterior column was much higher in our plate, indicating its inferior capacity to unload posterior fixation devices in such a situation. Concluding, the biplane contoured pelvic plate was superior in fixing unstable pelvic fractures anteriorly; it had also the advantage of being extensile and allowed the insertion of a retrograde pubic ramus screw through the anterior holes

Augmentation of partially regenerated nerves by end-to-side side-to-side grafting neurotization: experience based on 8 late obstetric brachial plexus cases

With or without previous early neurotization, the brachial plexus in obstetric palsy regenerates partially leading to variable degrees loss of function and deformity necessitating secondary correction. Correction after latissimus dorsi to rotator cuff transfer is not maintained. Posterior shoulder dislocation occurs after humeral rotation osteotomies. Both presuppose some degree of shoulder abduction. Further, corrective surgery will not benefit a flail wrist. Improving muscle power is the solution. End-to-side neurorrhaphy allows neurotization of partially injured recipient nerves without downgrading already regained recipient muscle power, a technique we called nerve augmentation. The aim was to investigate the effect of nerve augmentation on improving motor power in late obstetric brachial plexus lesions. 8 obstetric brachial plexus palsy cases aged 3-7 years were operated upon and followed up for 4 years. 5 patients were C5, 6 ruptures C7, 8T1 avulsions; 1 a C5,6,7,8 rupture T1 avulsion and 1 a C5,6,8T1 rupture C7 avulsion; 1 presented to us 3 years having undergone neurotization at the age of 3 months for a C5,6,7 rupture, C8 T1 compression. Patients were evaluated for deformities, muscle function, cocontractions. Root avulsions were evaluated by CT cervical myelography and confirmed intraoperatively. Shoulder, elbow and hand functions were scored using the modified Gilbert shoulder and elbow evaluation scales, and the Raimondi hand evaluation scale respectively. All nerves to Grades 1-3 muscles were selected for neurotization. Nerves to Grade 0 muscles were neurotized, if the electromyogram showed scattered motor unit action potentials on voluntary contraction without interference pattern. After exploration, the following donor nerves were selected for intertwining neurotization or closed loop grafting 25: The phrenic [7 cases], the accessory [2 cases], the descending and ascending loops of the ansa cervicalis [2 cases] and the 3[rd] and 4[th] intercostals [1 case]. Long length contact contralateral C7 neurotization [25] was performed in 5 cases. In the revision case, an external rotation humeral osteotomy and a Hoffer transfer preceded neurotization. Superior proximal to distal regeneration was observed firstly, shoulder and elbow muscles improving more than forearm, wrist and finger muscles. Differential regeneration of muscles supplied by the same nerve was observed secondly, the supraspinatus muscle regenerating superior to the infraspinatus. Differential regeneration of antagonistic muscles was observed thirdly; there was superior biceps to triceps and pronator teres to supinator recovery. Differential regeneration of fibres within the same muscle was observed fourthly, the anterior and middle fibres of the deltoid muscle regenerating better than its posterior fibres. Differential regeneration of muscles having different preoperative motor powers was noted fifthly. Functional improvement [i.e. to Grade 3 or more] in the forearm and hand occurred more in Grade 2 than in Grade 0 or Grade 1 muscles. Improvements of cocontractions and of shoulder, forearm and wrist deformities were noted sixthly. The shoulder, elbow and hand scores improved in 4 cases. First, the sample size is small [8 cases]. Second, controls are necessary to rule out any natural improvement of the lesion. Third, there is marked intra- and interobserver variability in testing muscle power and cocontractions. Nerve augmentation improves muscle power in the biceps, pectoral muscles, supraspinatus, anterior and lateral deltoids, triceps and in Grade 2 or more forearm muscles. It is also expected to improve cocontractions. As it is less expected to improve infraspinatus power, it should be associated with a humeral derotation osteotomy and tendon transfer. Function to non improving Grade 0 or 1 forearm muscles should be restored by free muscle transplantation. Notwithstanding all of the above, end-to-side neurorrhaphy needs reconsideration. Donor and recipient nerve channel carrying capacities have to be increased by cotrophism, cotropism and cotransplantation. Cell biologic procedures for restoring recipient muscle mass should be contemplated. Level IV, prospective case series

Outcome of internal fixation for unstable pelvic fractures: a series of 30 cases

A clinical study was conducted with the aim of finding the best methods for fixing the different types of unstable pelvic ring injuries, assessing the functional outcome after the various techniques and types of implants used and the union rate of pelvic fractures. Thirty patients, 26 males and 4 females, with a mean age of 31 years underwent open reduction and internal fixation for pelvic ring injuries. The mechanisms of injury were all high-energy injuries, 11 patients were hit by motor vehicles [pedestrian accidents] [37%], 10 patients were involved in motor vehicle accidents [MVA] [33%], 3 patients had crushing injuries [10%], 3 patients fell from heights [10%], and 3 patients were involved in motorcycle accidents [10%]. Fractures were classified according to both Young [13,14] and Tile [1] classification systems. All patients were evaluated preoperatively using the st and ard radiographs: AP, inlet, and outlet views, and CT scans. The operative treatment consisted of a combination of anterior and posterior fixation in 20 cases, posterior internal fixation alone was used in 5 cases and anterior external fixation was added to posterior fixation in 5 cases. Postoperatively, patients were followed-up for a mean of 12 months [range 6-24 months] and were evaluated using the Majeed score [27]. Our results revealed the following. One patient died postoperatively. Radiologically, one had a poor result, 16 patients were excellent, 11 were good, and 2 had fair reductions. The mean Majeed [27] score was 82 [range 66-95] among the 29 patients, 21 patients scored 75 points or higher [72%], and 8 patients scored between 75 and 66 [28%], and one patient died 2 weeks postoperatively. We come to the following conclusions. Unstable pelvic fractures require an aggressive and well-planned therapeutic regimen. Combined anterior and posterior internal fixation is the optimal treatment for vertically and rotationally unstable fractures. Stabilization must be tailored to the individual fracture, the surgeon must be familiar with all the techniques and able to perform them confidently. Reduction to within 10mm seems to be adequate for functional results. Anterior symphyseal diastasis is best treated by internal fixation using a single 4.5mm reconstruction plate on the superior surface of the pubic bones with either 4.5mm cortical screws or 6.5mm cancellous screws, the approach used is a Pfannenstiel approach without cutting the rectii. Fractures of the pubic rami are usually stable and do not require an extensive surgical approach, so they are best treated by anterior external fixation with posterior fixation or bed rest until patient is able to perform straight leg raising. They should be fixed when present medially, and are associated with symphyseal diastasis requiring plate fixation. Sacroiliac joint dislocations or Denis zone I sacral fractures are best treated by percutaneous cannulated 7.0mm iliosacral screws in the supine position as this allows combining anterior fixation simultaneously. Denis zone II sacral fractures can either be treated by open reduction through a posterior para-median approach in the prone position. This method is preferred, since it allows removal of bony fragments from the foramina and avoids overcompression of the foramina and hence iatrogenic nerve injuries. Alternatively, percutaneous iliosacral screws can be used, in this case they must be fully threaded to avoid overcompression of the foramina. Denis zone III sacral fractures are actually spine fractures. SI fracture dislocations are best approached anteriorly with the patient supine and fixed with two 3-4 hole 4.5mm reconstruction plates with one screw in the sacral ala, and 2 screws in the iliac side. Iliac fractures associated with vertically and rotationally unstable fractures are best treated by 4.5mm cortical interfragmentary screws between the 2 tables supported by neutralizing 4.5mm reconstruction plates through an anterior or posterior iliac approach. Sacral bars allow for vertical displacement of the hemipelvis so should be reserved for use when the surgeon is not familiar with the technique of percutaneous iliosacral screw fixation. The 3.5mm reconstruction plates should be reserved for use in thin bones, or in female patients. For stabilization of the posterior pelvic ring injuries, the supine position is preferred whenever possible, especially in polytrauma situations. Using either anterior plating of the SI joint or percutaneous iliosacral screws is recommended. Percutaneous iliosacral lag screws can be performed quickly and safely, they can restore posterior alignment and accomplish stable fixation except in very comminuted sacral fractures; therefore the need for an open posterior approach is minimized. The surgeon should decide which fracture to fix first according to the patient and the fracture. Generally, percutaneous iliosacral screw fixation in the supine position allows simultaneous anterior open reduction, as after the pelvis has been reduced both anteriorly and posteriorly, radiographic images are taken, then iliosacral screws are inserted and the anterior plate is fixed. The same is applicable with the anterior approach to the SI joint

Synthesis of some new pyrazolones and benzimidazol-acetonitriles derived from xanthene

Alpha -cyano - [xanthen-9-yl]-hydrazides 2 were cyclised to give 3-amino-4 [substituted-xanthen-9-yl]-pyrazolo-5 [4H] ones 3. Benzimidazole -[9-xanthen] 2-acetonitrilss 7 were formed by condensation of benzimidazole jole-2-acetonitrile with xanthen-9-olea. 3 and 7 were pyrolysed under reduced pressure to give 9-substituted-xanthenes. Various classes of nitrogen hetegocydes such as benzimidazoles, pyrazolones and analogous hetegocydes have been previously prepared and investigated for their biological activities. The aim of this work is to synthesise such compounds in an attempt to obtain newer compounds of anticipated broad spectrum biological activities

Synthesis of some 3-cyano5,6-dihydropyridines-2-ones and their n-substituted derivatives

3-Cyano-5,6-dihydro-4,6-disubstituted-6-methylpyridin-2-ones [2a-d] were prepared by condensation of methyl ketones and ethyl cyanoacetate in a 2:1 molar ratio in presence of ammonium acetate. The obtained pyridones [2a] and 2b] add diethyl acetylenedicarboxylate, acrylonitrile and methyl acrylate to give the corresponding N-substituted derivatives 3, 4 and 5 respectively. Several reports have been published dealing with the reaction of ethyl cyanoacetate with c,[B-unsaturated ketones to give 3- cyano-4, 6-disubstituted pyridin-2- ones [1-7], some of which were found to possess a pronounced antimicrobial activity [6-7]. In the present work, some dihydropyridone derivatives and related compounds have been synthesized by the condensation of ethyl cyanoacetate with some methyl ketones

Newer halo-and hydroxy-aryl pyrazolines and pyrazoles and their infrared spectra

It is found that [la] reacts with one mole of phenylhydrazine in boiling ethanol to give the expected l,3,-diphenyl-5 [3.4-dichlorophenyl]-delta[2]-pyrazoline [2]. The latter is readily dehydrogenated with tetrachloro-o-benzo-quinone at room temperature within a few minutes reaction period to give l,3-diphenyl-5 [3,4-dichlorophenyl] pyrazole[3] in good yield, along with tetra-chlorocatechol in a manner similar to that described by Latif et al. [1], as shown in scheme [A]. Structure of [2] is based on analogy [2-3], analytical data, yellow colour, strong fluorescence characteristic of pyrazolines, as well as spectral features. Its I.R. spectrum lacks nu c=o, nu nh; meanwhile its U.V. spectrum includes two maxima [lambda[max] 245, E 13630; lambda[max]. 350 nm E, 14155 ethanol], and thus supporting the delta[2]- pyrazoline structure [4] and excluding a possible hydrazone formation. The pyrazole[3], in contrast to the parent pyrazoline lacks colour and the absorption in its U.V. spectrum; meanwhile its U.V. spectrum exhibits the expected wave band [lambda[max] 290 nm E, 7390 ethanol] supporting its structure; its I.R. spectrum lacks VG=O and shows VC=N at 1600 cm[-1]. In contrast to the propenone [la], the hydroxyphenyl analogue [Ib] reacts with phenylhydrazine in equimolar amounts under the same conditions to give the expected yellow l,3-diphenyl-5 [3,5-dichloro-2-hydroxyphenyl]-delta[2]-pyrazoline [4a], in addition to the colourless dihydropyrazole [9]. However, when an excess of phenylhydrazine is used, [9] is exclusively produced without possible isolation of [4a]. Structure of [9] is inferred from analytical data, lack of colour and spectral features. Its I.R. spectrum is devoid of nu c=o and includes a broad band in the 3400-3100 cm[-1] region for NH and OH functions. Meanwhile, its U.V. spectrum exhibits a fairly strong styrene like band [[lambda[max]255 nm, E,7580 ethanol] due to the PHC= CH chromophore and lacks long -wave absorption, and thus excluding a delta[2] pyrazoline structure. The production of [9] apparently proceeds through an initial enhanced conjugate addition of the hydrazine to the beta-unsaturated ketone, followed by intramolecular cyclization as shown in scheme [B], which is rather unusual and in contrast to the usual delta[2]-pyrazoline formation which proceeds through the initial 1,2 addition to the carbonyl function

Ankylosis of temporomandibular joint

Fourteen cases of ankylosis of the Temporo-Mandibular joint were studied. An operation of condylectomy with a modification of excision of the coronoid process, part of the ramus of the mandible and release of the fibrosed temporalis muscle was done. A final result of a freely mobile mandible and a mouth opening of 25-30 mms were obtained in all of the cases

Excision arthroplasty of the elbow joint: a follow-up study

Excision arthroplasty to mobilize ankylosed elbow joints was done in 38 cases. the anklosis was secondary to trauma, pyogenic arthritis and rheumatoid arthritis. The surgical technique and after care are described and the complications are recorded. Follow-up results were analysed. The main reasons for failure and poor results were postoperative infection; partial and complete reankylosis; marked instability of the elbow joint and muscle weakness

Comparison of results of treatment of hydrocele by surgery and sclerotherapy

A comparison has been made between a series of 35 cases with primary vaginal hydrocoeles treated by surgery with an incidence of complications of 20% haematoma, 14.2% sepsis, an average hospital stay of 12 and another 35 cases treated by tapping and sclerotherapy, an outpatient technique with good cure results, very low complication, less expenses and loss of work and no risk of anaesthesia