RIA / Vol. 37 / N.À 2 Study and evolution of the qualityof raw milk from dairy farms in thenorthwest of the province of Santa Feand south of the province of Santiagodel Estero, Argentina (1993 – 2009) REVELLI, G.R.1; SBODIO, O.A.2; TERCERO, E.J.2 A total of 10,704 raw milk samples from a bulk tank were collected on 55 dairy farms associated to the Coo- perativa Tambera y Agropecuaria Nueva Alpina Ltda. between 1993 and 2009. Physicochemical, microbiologicaland sanitary parameters were analyzed within the framework of the Comprehensive Milk Quality ImprovementProgram to determine the mean values that characterize the zone. The following values were found: Acidity:16.30 ± 0.96 °D, pH: 6.68 ± 0.04, Fat: 3.48 ± 0.24%, True Protein: 3.11 ± 0.12%, Lactose: 4.74 ± 0.16%, Ash:0.70 ± 0.09%, Total Solids: 12.18 ± 0.42%, Freezing Point: -0.530 ± 0.02 °C, Total Bacterial Count: 9.6 x 104± 2.2 x 105 CFU/ml, Somatic Cell Count: 407,000 ± 230,000 cells/ml and Antibiotic Residues: 99.64% Negative.The most significant correlations were: Fat vs Total Solids (r = 0.784; P < 0.001) and True Protein vs TotalSolids (r = 0.557; P < 0.001). The compositional quality of raw milk from dairy farms in the northwest of SantaFe and south of Santiago del Estero were studied over a period of 17 years and showed a significant improve-ment, particularly regarding the indicators that infer a high industrial value. Optimization of the producers' ma-nagement capacity and the operational quality of dairy farmers contributed to achieve these results.
There are many prescription drugs available to treat MS. There are disease modifying drugs that affect the long-term course of MS and other medications to treat a particular symptom. Disease Modifying Treatments (DMTs)
There are number of disease-modifying treatments (DMTs) which can reduce the
frequency and severity of clinical relapses.
The National Institution for Care Excellence (NICE) published guidelines in October
2014 for the management of multiple sclerosis. In these guidelines a relapse can be
diagnosed by a GP or neurologist if:
The person with MS has developed new symptoms or has a worsening of existing
symptoms, and these symptoms have lasted for more than 24 hours in the absence of
infection of any other cause after a stable period of a least 1 month.
The following DMTs are available for treatment of relapsing remitting multiple sclerosis,
CIS andwho are still experiencing relapses, and where
these relapses are the predominant cause of their increasing disability :-
Avonex - a weekly injection into the muscle.
Rebif – an injection three times a week subcutaneously (under the skin).
Betaferon – an injection every other day subcutaneously (under the skin).
Extavia – an injection every other day subcutaneously (under the skin).
Glatiramer acetate (Copaxone) - a daily injection subcutaneously (under the skin).
The following DMTs are additionally available for treatment of relapsing remitting multiple sclerosis: Fingolimod (Gilenya) - an oral tablet taken once a day.
Tecfidera (Dimethyl fumerate) - an oral tablet twice a day.
Teriflunomide (Aubagio) - taken orally once a day.
For more detailed information about DMTs, please see our Choices leaflet ‘Disease Modifying Treatments.
A monoclonal antibody that works in a different way to the above DMTs, by preventing
immune cells leaving the blood stream and entering areas of inflammation.
This is available for people on the NHS with rapidly evolving, severe relapsing remitting
MS. Rapidly evolving, severe RRMS is defined by two or more disabling relapses in
one year along with an increase of lesions as shown on an MRI.
Tysabri is a once a month intravenous infusion into a vein over a one hour period in a
registered infusion facility.
For more detailed information about Tysabri, please see our Choices leaflet ‘Tysabri'.
Alemtuzumab was originally licensed for the treatment of leukaemia. It is an anti-CD52
monoclonal antibody which kills T-cells, a type of lymphocyte involved in the MS
immune response. It basically ‘reboots' the immune system. Once the t-cells are killed
(lymphocytes) the system then repopulates, leading to a modified immune response
that no longer regards myelin and nerves as foreign.
The drug received NICE appraisal as an NHS treatment in May 2014 from NICE and in July 2014 from the Scottish Medicines Consortium (SMC). Other Drugs used in MS
Low Dose Naltrexone (LDN)
LDN has been used in the treatment of MS in the USA since 1985 but it is relatively new
in the United Kingdom. Naltrexone is a drug referred to as an opiate antagonist. Its
normal use is to treat opiate drug addicts addicted to drugs such as heroin; however
when taken to treat MS, the dose is much smaller. Those taking it have experienced a
range of benefits, including reduced spasm and fatigue, improvements in bladder
control, heat tolerance, mobility, sleep, pain, tremor and other symptoms. The two main
symptoms that appear to improve most significantly are muscle spasm and fatigue.
It is not recognised by the NHS as a proven treatment for MS symptoms and may not therefore be prescribed by a GP or neurologist easily. It can be purchased privately in the UK. For more information about LDN, please see our Choices leaflet ‘LDN'.
Licensed in the UK as a form of chemotherapy used in cancer treatment but can be
used to treat some forms of MS. Usually given to people who have not responded to
Copaxone or any of the Interferons. It is given at the Neurologist's discretion by
Steroids are sometimes used when a person experiences a relapse to help speed
recovery. Steroids can reduce inflammation in the CNS. They are usually administered
intravenously but sometimes orally. In short term use, side-effects are usually minor.
Long term use should be avoided as this can cause many side-effects including weight
gain, acne and cataracts. For this reason, NICE guidelines recommend only using
steroids three times a year.
This drug therapy is a formulation of 4-aminopyridine – a potassium channel blocker. It
is thought that it can enhance the conduction of messages in damaged nerve fibres by
blocking potassium leaks. It is generally prescribed for people with MS who have MS
related mobility problems. Taken twice a day, fampridine is a licensed treatment to
improve walking speed.
Fampridine is not recommended by the Scottish Medicines Consortium (SMC).
In October 2014 the National Institute of Care Excellence published clinical guidelines
for the treatment of multiple sclerosis. In these guidelines, NICE states that fampridine
should not be offered to treat a lack of mobility in people with MS. This recommendation
does not apply to people who have already started treatment with fampridine in the NHS
who should be able to continue treatment until they and their NHS clinician think it
appropriate to stop.
Drugs in development and trial
The average time it takes for a new compound to get from the test tube to be licensed is
10 to 15 years. It is important to remember that not all these drugs will complete the
development process and be licensed for general use or be recommended by NICE
(National Institute for Health and Care Excellence) or the SMC (Scottish Medicines
Drugs used to manage symptoms
Bladder Dysfunction – see our Choices leaflet ‘Bladder & Bowel' for further
Oxybutynin is used to control urgent, frequent, or uncontrolled urination in people who have overactive bladder (a condition in which the bladder muscles have uncontrollable spasms) or other conditions that affect the bladder muscles. Oxybutynin is in a class of medications called anticholinergics. It works by relaxing the bladder muscles to prevent urgent, frequent, or uncontrolled urination. Desmopressin
Desmopressin is a synthetic antidiuretic hormone, which basically means that it supresses the production of urine in the kidneys by up to 8 hours. It is used to help relieve urinary incontinence in conditions such as MS. More specifically, it is used for those who experience ‘nocturia', the need to frequently go to the toilet at night. It can also be used during the day if finding a toilet may be difficult. For example, on a long journey. It should not be over-used due to the dangers of retaining too much urine. Detrusitol (Tolterodine)
Tolterodine is used to relieve urinary difficulties, including frequent urination and inability to control urination. Tolterodine is in a class of medications called antimuscarinics. It works by preventing bladder contraction. Botox
Botulinum toxin type A (Botox) is best known as a cosmetic treatment for facial wrinkles. Doctors have also found that botulinum toxin is useful in blocking spasms like eye ticks or relaxing muscles in patients with multiple sclerosis. Urologists have found that injecting botulinum toxin into the tissue surrounding the sphincter can help it to relax. Botox for the bladder was approved by the MHRA in September 2012 for those who have failed on existing treatments such as anticholinergics. Fatigue – see our Choices leaflet ‘Fatigue' for further information.
Amantadine is used to treat Parkinson's disease and conditions similar to those of Parkinson's disease. This medication is sometimes prescribed for other uses such as fatigue in multiple sclerosis. Spasticity - see our Choices leaflet ‘Symptoms' for further information.
Baclofen acts on the spinal cord nerves and decreases the number and severity of muscle spasms caused by multiple sclerosis or spinal cord diseases. It also relieves pain and improves muscle movement. Dantrolene
Dantrolene is used to treat chronic (long-term) muscle spasm or spasticity. Long-term muscle stiffness can occur in multiple sclerosis and other conditions where there has been damage to the nerves that supply the muscles. In these cases, muscles may contract (or shorten) tightly, they can then become stiff and harder to use. This is called spasticity. Dantrolene works by relaxing the muscles and preventing spasms. This helps to reduce any pain and discomfort. Diazepam
Diazepam is a type of medicine called a benzodiazepine. Benzodiazepines are used for their sedative, anxiety-relieving and muscle-relaxing effects. Diazepam works by acting on receptors in the brain called GABA receptors. This causes the release of a neurotransmitter called GABA in the brain. Botox
Zanaflex tablets contain the active ingredient tizanidine, which is a type of medicine known as an alpha-2-adrenoceptor agonist. Tizanidine is used as a muscle relaxant, in conditions such as multiple sclerosis and spinal cord injury or disease. Sativex
Sativex is a cannabis-based medicine used by people with MS for spasticity, when first line drugs have been ineffective or where side effects of those drugs are intolerable. It is an oral-mucosal spray into the mouth, under the tongue or inside of the cheeks. The number of sprays or timings of these sprays varies dependent on severity of symptoms and will be confirmed by the prescribing doctor. The maximum number of sprays a day is 12 and a gap of at least 15 minutes should be left between sprays. The most common side effects are dizziness, fatigue, drowsiness and nausea.
In October 2014 the National Institute of Care Excellence published clinical guidelines for the treatment of multiple sclerosis. In these guidelines, NICE states that Sativex should not be offered to treat spasticity in people with MS. Sativex may still be available through the NHS if funding is secured through an Individual Funding Request, although such a request is less likely to be successful in the light of the NICE guidelines. Sativex can be purchased privately if a private prescription is obtained from a GP. Tremor – see our Choices leaflet on ‘Symptoms' for further information.
Syprol oral solution contains the active ingredient propranolol, which is a type of medicine called a beta-blocker. Beta-blockers work by blocking beta receptors that are found in various parts of the body. Blocking beta receptors prevents the action of two chemicals, called noradrenaline and adrenaline, which are produced naturally by the body. Beta-blockers may have some effect on reducing MS related tremor. Primidone (Mysoline)
Primidone is a medicine which is used in partial epilepsy, generalised epilepsy, myoclonus and essential tremor. Mysoline tablets contain the active ingredient primidone. Clonazepam (Rivotril)
Rivotril tablets and injections both contain clonazepam, which is a type of medicine called a benzodiazepine. Clonazepam is also available without a brand name, i.e. as themedicine. Clonazepam acts on nerve cells in the brain. Clonidine
Clonidine is thought to reduce the responsiveness of small blood vessels to stimuli which would normally make them contract (narrow) or dilate (widen). This prevents the changes in the blood vessels of the brain which are associated with migraine, and thus prevents attacks. Pain – see our Choices leaflet on ‘Pain' for further information.
The way in which gabapentin works is not fully understood. It is thought to work by binding to calcium channels found on nerve cells in the brain and spinal cord. This is thought to affect the release of various neurotransmitters from these nerve cells.
The way in which pregabalin works is not fully understood. It is thought to work by binding to calcium channels found on nerve cells in the brain and spinal cord. This reduces the release of various neurotransmitters from these nerve cells. Carbamazepine
Carbamazepine is an anticonvulsant. It works by decreasing nerve impulses that cause seizures and pain. Carbamazepine is used to treat seizures and nerve pain such as trigeminal neuralgia and diabetic neuropathy. It is also used to treat bipolar disorder. Amitriptyline
Amitriptyline is a tricyclic antidepressant. It affects chemicals in the brain that may become unbalanced. Amitriptyline is used to treat symptoms of depression. Duloxetine
Duloxetine is a serotonin-norepinephrine reuptake inhibitor, affecting chemicals in the brain that may be unbalanced. Duloxetine is used to treat symptoms of depression and generalised anxiety disorder, but can relieve the symptoms of neuropathic pain. Erectile Dysfunction – see our Choices leaflet on ‘Sexual Dysfunction' for further
Cialis (Tadalafil) relaxes muscles and increases blood flow to particular areas of the body. Cialis is used to treat erectile dysfunction (impotence) in men. Viagra
Viagra (sildenafil) relaxes muscles and increases blood flow to particular areas of the body. Viagra is used to treat erectile dysfunction (impotence) in men. Levitra
Levitra (Vardenafil) is a phosphodiesterase inhibitor. It works by helping to relax muscles and increase blood flow into the penis during sexual stimulation. This helps men to achieve and maintain an erection. Levitra is used to treat erectile dysfunction (impotence). Updated October 2014
Multicenter phase ii trial of bendamustine in combination with rituximab for patients with relapsed chronic lymphocytic leukemia
FCR versus BR in first line therapy of CLL 1. PROTOCOL SYNOPSIS CLL10 protocol of the German CLL-Study Group (GCLLSG) Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) alone in patients with previously untreated chronic lymphocytic leukaemia