Tumoricidal Activation of Macrophages using Jatropha curcas Leaf Extract

Biological activities of the methanolic was under study. Leaf extracts that contains methanolic acid of Jatropha curcas showed the highest antioxidant activity. Other research in cytotoxicity assay results indicated the anticancer therapeutic property of the root extract against human colon adenocarcinoma (HT-29) cell line but its cytotoxic effect on human hepatocyte (Chang cell) was high.

Macrophages can be activated to become neoplasticidal by interaction with a substance filled immune modulators. Neoplasticidal macrophages can recognize and destroy neoplastic cells in vitro and in vivo. Although the exact mechanism by which macrophages discriminate between neoplastic and normal cells is unknown, it is independent of neoplastic cell characteristics such as immunogenicity, metastatic potential, and sensitivity to drugs. 

Moreover, macrophage destruction of neoplastic cells apparently is not associated with the development of neoplastic cell resistance. Macrophages are found in association with neoplasm in a definable pattern, suggesting that the most direct way to achieve macrophage-mediated neoplasm regression is in situ macrophage activation.

Thiram is widely used as a dithiocarbamate pesticide and fungicide, but can also be used as a suppressor of inflammation; studies have shown that thiram can reduce the inflammation resulting from contact dermatitis. Explain when thiram interact with the agency and the intensity of the inflammation will decline.

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Postmenopausal Women: A Meta-Analysis

Osteoporosis is a progressive bone disease that is characterised by a decrease in bone mass and density and that leads to an increased risk of fracture. In osteoporosis, the bone mineral density (BMD) is reduced, bone microarchitecture deteriorates, and the amount and variety of proteins in bone are altered. Both environmental and genetic factors are the etiology of osteoporosis. In addition, family and twin studies show that osteoporosis is a multi-gene regulation, strong hereditary diseases. Osteoporosis and osteoporotic fractures had brought serious harms to families and societies due to its high incidence, mortality, and medical costs.

The early identification of a person who is at risk to develop osteoporotic fractures is therefore of major clinical interest. Morrison’s study have shown that vitamin D receptor has been associated with Bone Mineral Density (BMD), which is the major determinant of osteoporosis risk. Since then, many factors about the relationship between gene polymorphism, BMD and fracture were intensively investigated, such as typecollagen gene, calcitonin receptor gene, low-density lipoprotein receptor related protein gene and cannabinoid receptor genes. However, vitamin D receptor gene is the most studied and controversial gene.

Vitamin D receptor gene is located on chromosome 12, longer than 100 kb. Through the genome of a single nucleotide polymorphism frequency analysis, the vitamin D receptor gene polymorphism should be more than 100 kinds. We know vitamin D receptor gene polymorphisms mainly related to four single nucleotide polymorphisms (BsmI, TaqI, ApaI and FokI) from recent study. Fang et al. performed a meta-analysis relating BsmI or TaqI polymorphisms of the VDR gene with Osteoporosis risk. They searched published studies from 1996 to September 2005 through PubMed and evaluated the genetic effect of the BsmI and TaqI polymorphism of VDR on fracture risk and found out that there was no relationship between the VDR BsmI or TaqI polymorphism and fracture risk.

Self-Fulfilling Diagnoses

A young lady 23 years of age, recently reported to her orthopedic surgeon complaining of pain in the right hip. Because it was summertime and warm, she wore shorts to the appointment. An obvious rash could be seen in the area where there was pain. An X-ray revealed no contributing factors. The surgeon prescribed physical therapy, with the comment that if the pain did not resolve, an MRI would be ordered.

Four days later, the pain had intensified to the degree that the patient fainted at work and was sent to the ER. An extensive work-up including MRI and ultrasound took all day, yet there was no diagnosis made by the team of ER physicians. The patient was sent home with a prescription for analgesics, and advised to wait.

The next day, “D” walked into a local clinic because the discomfort associated with the rash persisted and she hoped that at least this condition could be treated. The primary care physician on call took one look and immediately diagnosed herpes zoster. The diagnosis explained the symptoms: pain, rash, and itch. Unfortunately, the diagnosis was made too late for an effective course of antivirals and “D” continued to suffer for another few weeks although the pain and itch steadily diminished in severity.

Percutaneous Bunionette Correction

This study used 24 lower limbs from 12 fresh frozen cadavers. The specimens were obtained via the Human Body Donation programme of the University. Specimens with previous foot surgery or trauma have been excluded. All surgery was performed by two surgeons. One surgeon was a foot and ankle surgeon with over 5 years of experience with percutaneous surgery. The second surgeon was a 4th-year registrar in the speciality of orthopaedic surgery. The experience in percutaneous foot surgery was limited to one training session on cadaveric specimens.

The procedures were carried out in a cadaveric lab. The limbs were positioned on standard dissection tables and thawed 24 hrs prior to the experiments. The first 16 surgeries were performed by the first (experienced) surgeon, the other 8 surgeries were performed by the second surgeon.

The skin incision was performed using a Swann Morton 64 Beaver mini blade. A Shannon 44 Long burr was connected to an electrical power driven system of the “de Prado” type. The base power was controlled by a foot pedal allowing the surgeon to keep his hands free for surgery. The osteotomy was performed by making a supination movement with the dominant hand holding the Shannon 44 Long burr. The maximum speed of the burr was 7000 rpm. According to the dominant hand of the surgeon, the technique was slightly different when operating on the right or left foot. Both surgeons were right-handed. When performing surgery on a right foot, the incision was slightly medial to the shaft of the metatarsal on the distal third of the diaphysis.

Journal of Bone Reports & Recommendations

The Journal of Bone Reports & Recommendations is an open access, interdisciplinary journal for the rapid publication of original articles and reviews that focus on basic research in all areas of bone such as mineral metabolism, interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems, bone remodeling, musculoskeletal disorders and other relevant fields.

Open access is a pioneering publishing model wherein all articles published in this journal will be available online, to anyone, anywhere in the world, completely free of charge. Articles once submitted to the journal are peer-reviewed carefully. Once accepted, articles are then proof-read for publication and published online where they are freely accessible without any subscription.

The aim of this Journal is to publish high quality articles on related aspects of public health, health policy and clinical analysis which can improve health care and outcomes for persons suffering from bone diseases, moreover mitigate the conditions related to bone disorders globally.

Bone oncology may be classified as "primary tumors", which originate in bone or from bone-derived cells and tissues, and "secondary tumors" which originate in other sites and spread (metastasize) to the skeleton. Carcinomas of the prostate, breasts, lungs, thyroid and kidneys are the carcinomas that most commonly metastasize to bone. Secondary malignant bone tumors are estimated to be 50 to 100 times as common as primary bone cancers.

Percutaneous Repair of Acute Closed Rupture of Achilles Tendon

Rupture of the Achilles tendon is increasingly common, and an incidence of 18 per 100,000 has been reported. The Achilles tendon is the strongest tendon in the human body which takes its name from Achilles, from Homer’s Iliad. Hippocrates said “this tendon, if bruised or cut, causes the most acute fevers, induces choking, deranges the mind and at length brings death”. Since Ambroise Paré initially described in 1575 and reported in the literature in 1633, Achilles tendon breakage has received a lot of attention.

The current treatment options can be classified as non-operative (casting or functional bracing) or operative. Although some authors recommend conservative management strongly, cast immobilization may lead to elongation of the tendon with reduced strength of the calf muscles and in a high rate of re-rupture.

As a common concept, operative regiments present a lower rerupture rate, early functional rehabilitation, stronger push off with lower incidence of calf atrophy. But open surgical repair of the Achilles tendon also includes potential problems like joint stiffness, muscles atrophy, tendo-cutaneous adhesions, deep venous thrombosis due to prolonged immobilization after surgical repair, infection, scarification, and wound breakdown

Minimal Invasive Percutaneous Repair of Acute Closed Rupture of Achilles Tendon

Rupture of the Achilles tendon is increasingly common, and an incidence of 18 per 100,000 has been reported. The Achilles tendon is the strongest tendon in the human body which takes its name from Achilles, from Homer’s Iliad. Hippocrates said “this tendon, if bruised or cut, causes the most acute fevers, induces choking, deranges the mind and at length brings death”. Since Ambroise Paré initially described in 1575 and reported in the literature in 1633, Achilles tendon breakage has received a lot of attention.

The current treatment options can be classified as non-operative (casting or functional bracing) or operative. Although some authors recommend conservative management strongly, cast immobilization may lead to elongation of the tendon with reduced strength of the calf muscles and in a high rate of re-rupture.

As a common concept, operative regiments present a lower rerupture rate, early functional rehabilitation, stronger push off with lower incidence of calf atrophy. But open surgical repair of the Achilles tendon also includes potential problems like joint stiffness, muscles atrophy, tendo-cutaneous adhesions, deep venous thrombosis due to prolonged immobilization after surgical repair, infection, scarification, and wound breakdown.

Percutaneous repair was described in 1977 by Ma and Griffith with no re-ruptures and only two minor complications; these have led some authors to develop new and alternative methods of percutaneous repair. Percutaneous or minimally invasive techniques are being used to minimize the typical complications associated with open surgery, and results are reported to be satisfactory, but an increased incidence of sural nerve injury has been reported after percutaneous repair.

Biosimilars in Rheumatology: General Issues

The European Union has led the way in establishing regulations for biosimilars. In 2005, the EMA established the first regulatory pathway for biosimilars that is distinct from the generic pathway [9-13]. The biosimilar manufacturer should assemble all available knowledge of the reference product with regard to the type of host cell, formulation and container closure system, and submit a complete description and data package delineating the whole manufacturing process including obtaining and expression of target genes, the optimization and fermentation of gene engineering cells, the clarification and purification of the products, the formulation and testing, aseptic filling and packaging.

Furthermore, non-clinical evaluations should be undertaken both in vitro and in vivo. In terms of the clinical evaluation, the comparability exercise should begin with pharmacokinetic (PK) and pharmacodynamic (PD) studies followed by the pivotal clinical trials. PK studies should be designed to enable detection of potential differences between a biosimilar and the reference product. Singledose, cross-over PK studies in homogenous population are recommended.

The manufacturer should justify the choice of singledose studies, steady-state studies, or repeated determination of PK parameters and the study population. PD studies and confirmatory PK/PD studies may be appropriate if there are clinically relevant PD markers, but if there is lack of them, the traditional 80-125% equivalence range is often used. In addition, similar efficacy of biosimilar and reference product has to be demonstrated in randomized and well controlled clinical trials, which should preferably be double blind or at least observer blind. The pre licensing safety data and the immunogenicity data should be obtained from the comparative efficacy trials. Finally, applicants also need to present an ongoing risk management and pharmacovigilance plan, since data from pre-authorized clinical studies are usually too limited to identify all potential side effects of the biosimilar.

Clinical management

Due to their special characteristics, there is the need to pay even more attention when using biosimilars than when using small chemicals. Most biopharmaceuticals induce immune responses, which in many cases do not have clinically relevant consequences but in some situations the consequences can be more relevant and potentially lethal, causing a loss of efficacy of the drug or even leading to autoimmunity to endogenous molecules. The immunogenicity to biopharmaceuticals is based on their foreign nature, being of exogenous origin (neo-antigens or non-self antigens) or in their similarity to self molecules (self antigens). Anyway, it is the activation of antibody-secreting B cells which is the main reason that causes the clinical manifestation of immunogenicity. There are two ways in which such immunogenicity can occur. On the one hand, impurities, such as endotoxins or denatured proteins within a biopharmaceutical may provide a signal to T cells, that may then send activating signals to B cells and hence, break B cell tolerance. On the other hand, B cell tolerance can be broken via a T cell independent response. If a biopharmaceutical is not uniformly soluble it can form aggregates and they can be confused with viruses, activating B cells to produce auto reactive binding antibodies

Reconstruction of Lateral Ankle Ligaments Update

Lateral ligament insufficiency secondary to ankle sprain is one of the most frequently encountered musculoskeletal injuries. Such an insult typically occurs following a combined inversion-plantar flexion injury of the foot, which often leads to disruption of the lateral ligamentous complex. While most fully recover, up to 20% of patients experience long-lasting symptoms following the initial event, such as stiffness, ligament laxity, weakness, and recurrent sprains– all of which pave the way for chronic ankle instability. Left unaddressed, lack of joint stability can initiate a cascade of undesirable complications, such as chronic pain, synovitis, chondral damage, and osteoarthritis. Treatment with conservative modalities, such as functional rehabilitation, muscle strengthening, and proprioceptive training, is often successful, particularly in cases of functional instability alone (subjective feeling of one’s ankle “giving out”). For patients that develop chronic instability and fail to achieve satisfactory outcomes with a conservative treatment regimen, surgical intervention is often indicated.

Anatomically, chronic lateral ankle instability is often due to compromise of the anterior joint capsule and the anterior talofibular ligament (ATFL), with additional insufficiency of the calcaneofibular ligament (CFL) in about 15%-30% of patients. Ligamentous repair of the lateral ankle is typically classified as non-anatomic or anatomic. While non-anatomic procedures usually achieve successful reconstruction outcomes, these techniques have been linked to abundance of undesirable post-surgical complications; as such, anatomic reconstruction, in particular the modified Brostrom-Gould method is considered by many orthopedic surgeons to be the superior reconstructive technique for repair of the aforementioned ligaments. 

Yet while the modified Brostrom has proven both reliable and highly effective, clinical studies show that anywhere from 13% to 35% of patients experience residual symptoms following successful anatomic reconstruction as a result of unaddressed intra-articular lesions.

Spinal Trauma in Italy: Actuality and Future Perspectives

According to the current literature, the incidence of spinal trauma with neurological impairment in Italy is estimated to be between 18 and 20 cases per million. Usually the most affected patients are young or middle aged, with a male/female ratio of 3,5-4,1 and the trauma is related to road accidents. Spine trauma is also related to work accidents: falls from a height in 53% of the cases, road accidents during the drive to and from work in 20% of cases. In the elderly population, the main cause is due to home accidents. Spinal Cord Injuries (SCI) are between the main reasons of permanent disability, with a high economic and social expense; their incidence is increasing, due to the different lifestyle and the augmented life expectancy.

Primary prevention could reduce the global incidence of spinal cord injuries. Secondary prevention, with a correct diagnosis and treatment in the early phase might reduce the number of negative outcomes, and improve the quality of life of the patients with SCI. A careful clinical and radiological assessment, associated with an early surgical treatment, are of main importance to improve the prognosis of the patient. The clinical outcome of SCI patients might be improved in specialized centres, with intensive care unit and specific trauma management protocols.

Actuality and future perspectives

According to Fehlings et al. all patients with SCI are at high risk for cardiovascular and respiratory complicances. Moreover the management of patients with acute SCI, whenever possible, in specialized centres is fundamental. In Italy, patients with SCI might refer to different types of structures. The Unipolar Spinal Unit (USU) is a sanitary structure where all the specialists needed for the management of SCI are involved in the same place.

In the Bipolar Spinal Unit (BSU) the emergency phase and the post-acute phase are held in different places. The Dedicated Centres are structures compared to Spinal Units in which the rehabilitative phase is held. The USU represents, therefore, the medical centre of excellence, due to their capability of multidisciplinary management of the patient with SCI. Many specialists are involved and cooperate, such as the neurosurgeon, the neurologist, the anesthetist and the physiotherapist.

Is the Short Posterior Stabilization by TLIF and Cages A Good Way for A Correct Spinal Alignment in the De Novo Scoliosis? A Case Report

Scoliosis is a medical condition in which a person’s spinal axis has a three-dimensional deviation. The main diagnostic criterion is spinal curvature exceeding 10° on a plain antero-posterior X-ray image. Scoliosis can occur before skeletal maturity and persist over time (idiopathic scoliosis) or it can occur in adulthood (de novo scoliosis). “De novo scoliosis” is due to disc degeneration, osteoporosis, and osteoarthritis of the facet joints.“Idiopathic scoliosis” represents temporal continuity of a spinal deformity, and is already present in prepuberty or adolescence. It normally becomes symptomatic with disc degeneration. Although the etiology of these conditions is different, they can coexist and overlap .The incidence of scoliosis in people over fifty years of age is 6 percent, and in patients over fifty years of age with osteoporosis or osteomalacia, the incidence is six times greater and there is a higher risk of health problems in adult life, decreased quality of life, cosmetic deformity and visible disability, pain and progressive functional limitations . We reported a case of de novo scoliosis treated with short stabilization technique and TLIF in accord with Harms and Jeszensky.

Case Presentation

Our patient,a74 year old retired bank worker, came to the center of our Spine Surgery AOUS University Policlinic “Santa Maria alle Scotte” of Siena, reporting an anamnestic history of backache for 6 months, and was negative for idiopathic scoliosis. He reported an ingravescent limitation in the performance of daily activities. Pain measured by VAS scale was an 8,while the Oswestry Low Back Pain Score was 36 points and 46 in SF-36 scale.Upon objective examination the patient had an unnatural upright posture while squatting, and there was a scoliotic deflection along the thoracic, thoraco-lumbar, lumbar, and lower back section, with the presence of a rib prominence. 

The patient also had left radicular syndrome. He had an intermittent claudicatio with pain after 25 meters of walk. The vertebrae with a limiting curve were T12 andL5, while theapical vertebra was L2.X-ray measurement in AP projection (antero-posterior) revealed that the patient had an angle of 22.8° Cobb (between upper surface of T12 and lower of L5) while the LL (latero-lateral) projection (Figure 2) was 15.7° Cobb, with the loss of the physiological lumbar lordosis.